Sodium channel - Knowledge

425:. The inactivation gate can be thought of as a "plug" tethered to domains III and IV of the channel's intracellular alpha subunit. Closure of the inactivation gate causes Na flow through the channel to stop, which in turn causes the membrane potential to stop rising. The closing of the inactivation gate creates a refractory period within each individual Na channel. This refractory period eliminates the possibility of an action potential moving in the opposite direction back towards the soma. With its inactivation gate closed, the channel is said to be inactivated. With the Na channel no longer contributing to the membrane potential, the potential decreases back to its resting potential as the neuron repolarizes and subsequently hyperpolarizes itself, and this constitutes the falling phase of an action potential. The refractory period of each channel is therefore vital in propagating the action potential unidirectionally down an axon for proper communication between neurons. 244:, this segment moves toward the extracellular side of the cell membrane, allowing the channel to become permeable to ions. The ions are conducted through the central pore cavity, which consists of two main regions. The more external (i.e., more extracellular) portion of the pore is formed by the "P-loops" (the region between S5 and S6) of the four domains. This region is the most narrow part of the pore and is responsible for its ion selectivity. The inner portion (i.e., more cytoplasmic) of the pore is the pore gate and is formed by the combined S5 and S6 segments of the four domains. The pore domain also features lateral tunnels or fenestrations that run perpendicular to the pore axis. These fenestrations that connect the central cavity to the membrane are proposed to be important for drug accessibility. 1540:

that decrease the blood pH, such as exercising, the probability of channels activating and inactivating is higher more positive membrane potentials, which can lead to potential adverse effects. The sodium channels expressed in skeletal muscle fibers have evolved into relatively pH-insensitive channels. This has been suggested to be a protective mechanism against potential over- or under-excitability in skeletal muscles, as blood pH levels are highly susceptible to change during movement. Recently, a mixed syndrome mutation that causes periodic paralysis and myotonia in the skeletal sodium channel has been shown to impart pH-sensitivity in this channel, making the gating of this channel similar to that of the cardiac subtype.

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of calcium and potassium channels. Instead, they are homologous to neural cell adhesion molecules (CAMs) and the large family of L1 CAMs. There are four distinct betas named in order of discovery: SCN1B, SCN2B, SCN3B, SCN4B (table 2). Beta 1 and beta 3 interact with the alpha subunit non-covalently, whereas beta 2 and beta 4 associate with alpha via disulfide bond. Sodium channels are more likely to stay open at the subthreshold membrane potential when interacting with beta toxins, which in turn induces an immediate sensation of pain.

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diverse set of changes to sodium channel gating, which generally lead to decreases in the amplitude of the transient sodium current and increases in the fraction of non-inactivating channels that pass persistent currents. These effects are shared with disease-causing mutants in neuronal, skeletal muscle, and cardiac tissue and may be compounded in mutants that impart greater proton sensitivity to sodium channels, suggesting a role of protons in triggering acute symptoms of electrical disease.

519: 233:. An alpha subunit forms the core of the channel and is functional on its own. When the alpha subunit protein is expressed by a cell, it is able to form a pore in the cell membrane that conducts Na in a voltage-dependent way, even if beta subunits or other known modulating proteins are not expressed. When accessory proteins assemble with α subunits, the resulting complex can display altered voltage dependence and cellular localization. 210: 1427: 268:. In response to an increase of the membrane potential to about −55 mV (in this case, caused by an action potential), the activation gates open, allowing positively charged Na ions to flow into the neuron through the channels, and causing the voltage across the neuronal membrane to increase to +30 mV in human neurons. Because the voltage across the membrane is initially negative, as its voltage increases 1527:

motif. The permeation rate of sodium through the sodium channel is determined by a four carboxylate residues, the EEDD motif, which make up the outer charged ring. The protonation of these carboxylates is one of the main drivers of proton block in sodium channels, although there are other residues that also contribute to pH sensitivity. One such residue is C373 in the

978:. Voltage-gated sodium channels also assemble with a variety of other proteins, such as FHF proteins (Fibroblast growth factor Homologous Factor), calmodulin, cytoskeleton or regulatory kinases, which form a complex with sodium channels, influencing its expression and/or function. Several beta subunits interact with one or more 1517:

Changes in blood and tissue pH accompany physiological and pathophysiological conditions such as exercise, cardiac ischemia, ischemic stroke, and cocaine ingestion. These conditions are known to trigger the symptoms of electrical diseases in patients carrying sodium channel mutations. Protons cause a

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of a neuron is usually -60mV to -80mV, driven primarily by the K potential at -90mV. The depolarization from the K potential is due primarily to a small Na leak current. About 70% of this current is through NALCN. Increasing NALCN permeability lowers the resting membrane potential, bringing it closer

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The probable evolutionary relationship between these channels, based on the similarity of their amino acid sequences, is shown in figure 1. The individual sodium channels are distinguished not only by differences in their sequence but also by their kinetics and expression profiles. Some of this data

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that are affected by three independent gating variables. Each of these variables can attain a value between 1 (fully permeant to ions) and 0 (fully non-permeant), the product of these variables yielding the percentage of conducting channels. The Hodgkin–Huxley model can be shown to be equivalent to a

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Mutations to NALCN lead to severe disruptions to respiratory rhythm in mice and altered circadian locomotion in flies. Mutations to NALCN have also been linked to multiple severe developmental disorders and cervical dystonia. Schizophrenia and bipolar disorder are also linked to mutations to NALCN.

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Despite following the same basic structure as other sodium channels, NALCN is not sensitive to voltage changes. The voltage-sensitive S4 transmembrane domain of NALCN has fewer positively charged amino acids (13 instead of a voltage gated channel's 21) possibly explaining its voltage insensitivity.

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Sodium channel beta subunits are type 1 transmembrane glycoproteins with an extracellular N-terminus and a cytoplasmic C-terminus. As members of the Ig superfamily, beta subunits contain a prototypic V-set Ig loop in their extracellular domain. They do not share any homology with their counterparts

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When any kind of ion channel does not inactivate itself, it is said to be persistently (or tonically) active. Some kinds of ion channels are naturally persistently active. However, genetic mutations that cause persistent activity in other channels can cause disease by creating excessive activity of

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Beyder A, Mazzone A, Strege PR, Tester DJ, Saito YA, Bernard CE, Enders FT, Ek WE, Schmidt PT, Dlugosz A, Lindberg G, Karling P, Ohlsson B, Gazouli M, Nardone G, Cuomo R, Usai-Satta P, Galeazzi F, Neri M, Portincasa P, Bellini M, Barbara G, Camilleri M, Locke GR, Talley NJ, D'Amato M, Ackerman MJ,

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As the cardiac sodium channel is the most pH-sensitive sodium channel, most of what is known is based on this channel. Reduction in extracellular pH has been shown to depolarize the voltage-dependence of activation and inactivation to more positive potentials. This indicates that during activities

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Single channel data from cardiomyocytes have shown that protons can decrease the conductance of individual sodium channels. The sodium channel selectivity filter is composed of a single residue in each of the four pore-loops of the four functional domains. These four residues are known as the DEKA

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NALCN complexes with the proteins UNC79, UNC80, and FAM155A. UNC79 appears to be linked to membrane stability of NALCN and linkage with UNC 80. UNC80 mediates chemical modulation of NALCN through multiple pathways. FAM155A helps protein folding in the endoplasmic reticulum, chaperones transport to

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Voltage-gated Na channels have three main conformational states: closed, open and inactivated. Forward/back transitions between these states are correspondingly referred to as activation/deactivation (between open and closed, respectively), inactivation/reactivation (between inactivated and open,

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Ligand-gated sodium channels, on the other hand, create the change in the membrane potential in the first place, in response to the binding of a ligand to it. Leak sodium channels additionally contribute to action potential regulation by modulating the resting potential (and in turn, the

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Al-Sayed, Moeenaldeen D.; Al-Zaidan, Hamad; Albakheet, Albandary; Hakami, Hana; Kenana, Rosan; Al-Yafee, Yusra; Al-Dosary, Mazhor; Qari, Alya; Al-Sheddi, Tarfa; Al-Muheiza, Muhammed; Al-Qubbaj, Wafa; Lakmache, Yamina; Al-Hindi, Hindi; Ghaziuddin, Muhammad; Colak, Dilek (2013-10-03).

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Voltage-gated sodium channels normally consist of an alpha subunit that forms the ion conduction pore and one to two beta subunits that have several functions including modulation of channel gating. Expression of the alpha subunit alone is sufficient to produce a functional channel.

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Sodium leak channels do not show any voltage or ligand gating. Instead, they are always open or "leaking" a small background current to regulate the resting membrane potential of a neuron. In most animals, a single gene encodes the NALCN (sodium leak channel, nonselective) protein.

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Sodium channels are highly selective for the transport of ions across cell membranes. The high selectivity with respect to the sodium ion is achieved in many different ways. All involve encapsulation of the sodium ion in a cavity of specific size within a larger molecule.

181:. These channels go through three different states called resting, active and inactive states. Even though the resting and inactive states would not allow the ions to flow through the channels the difference exists with respect to their structural conformation. 3105:

Grolleau F, Stankiewicz M, Birinyi-Strachan L, Wang XH, Nicholson GM, Pelhate M, Lapied B (February 2001). "Electrophysiological analysis of the neurotoxic action of a funnel-web spider toxin, delta-atracotoxin-HV1a, on insect voltage-gated Na+ channels".

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The family of sodium channels has 9 known members, with amino acid identity >50% in the trans-membrane segments and extracellular loop regions. A standardized nomenclature for sodium channels is currently used and is maintained by the

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Noland, Cameron L.; Chua, Han Chow; Kschonsak, Marc; Heusser, Stephanie Andrea; Braun, Nina; Chang, Timothy; Tam, Christine; Tang, Jia; Arthur, Christopher P.; Ciferri, Claudio; Pless, Stephan Alexander; Payandeh, Jian (17 March 2022).

4010:"On the structural basis for size-selective permeation of organic cations through the voltage-gated sodium channel. Effect of alanine mutations at the DEKA locus on selectivity, inhibition by Ca2+ and H+, and molecular sieving" 631:), intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), Panayiotopoulos syndrome, familial hemiplegic migraine (FHM), familial autism, Rasmussens's encephalitis and Lennox-Gastaut syndrome 2451:

Isom LL, De Jongh KS, Patton DE, Reber BF, Offord J, Charbonneau H, Walsh K, Goldin AL, Catterall WA (May 1992). "Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel".

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In mammalian sodium channels, the region linking domains III and IV is also important for channel function. This DIII-IV linker is responsible for wedging the pore gate shut after channel opening, inactivating it.

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Swayne, Leigh Anne; Mezghrani, Alexandre; Varrault, Annie; Chemin, Jean; Bertrand, Gyslaine; Dalle, Stephane; Bourinet, Emmanuel; Lory, Philippe; Miller, Richard J.; Nargeot, Joel; Monteil, Arnaud (2009-07-03).

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Rush AM, Wittmack EK, Tyrrell L, Black JA, Dib-Hajj SD, Waxman SG (May 2006). "Differential modulation of sodium channel Na(v)1.6 by two members of the fibroblast growth factor homologous factor 2 subfamily".

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Yeh, Edward; Ng, Sharon; Zhang, Mi; Bouhours, Magali; Wang, Ying; Wang, Min; Hung, Wesley; Aoyagi, Kyota; Melnik-Martinez, Katya; Li, Michelle; Liu, Fang; Schafer, William R.; Zhen, Mei (2008-03-11).

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Mok, Kin Y.; Schneider, Susanne A.; Trabzuni, Daniah; Stamelou, Maria; Edwards, Mark; Kasperaviciute, Dalia; Pickering-Brown, Stuart; Silverdale, Monty; Hardy, John; Bhatia, Kailash P. (2014-02-01).

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Gamal El-Din, Tamer M., et al. "Fenestrations control resting-state block of a voltage-gated sodium channel." Proceedings of the National Academy of Sciences 115.51 (2018): 13111-13116.

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S4 segment acts as the channel's voltage sensor. The voltage sensitivity of this channel is due to positive amino acids located at every third position. When stimulated by a change in

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At the peak of the action potential, when enough Na has entered the neuron and the membrane's potential has become high enough, the Na channels inactivate themselves by closing their

549:, does not act in a voltage-gated way. It has a loosely similar overall structure. Not much is known about its real function, other than that it also associates with beta subunits. 1419:

NALCN is also far less selective for Na ions and is permeable to Ca and K ions. The EEKE amino acid motif in the pore filter domain of NALCN is similar to both the EEEE motif of

432:. With the activation gate closed and the inactivation gate open, the Na channel is once again in its deactivated state, and is ready to participate in another action potential. 1859:

Tao, Elaine, and Ben Corry. "Characterizing fenestration size in sodium channel subtypes and their accessibility to inhibitors." Biophysical Journal 121.2 (2022): 193-206.

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respectively), and recovery from inactivation/closed-state inactivation (between inactivated and closed, respectively). Closed and inactivated states are ion impermeable.

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Humphrey, John A.; Hamming, Kevin S.; Thacker, Colin M.; Scott, Robert L.; Sedensky, Margaret M.; Snutch, Terrance P.; Morgan, Phil G.; Nash, Howard A. (2007-04-03).

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Lim C, Dudev T (2016). "Chapter 10. Potassium Versus Sodium Selectivity in Monovalent Ion Channel Selectivity Filters". In Astrid S, Helmut S, Roland KO S (eds.).

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The alpha subunit consists of four repeat domains, labelled I through IV, each containing six membrane-spanning segments, labelled S1 through S6. The highly

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associated to pass through. The larger K ion cannot fit through this area. Ions of different sizes also cannot interact as well with the negatively charged

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zero (from −70 mV at rest to a maximum of +30 mV), it is said to depolarize. This increase in voltage constitutes the rising phase of an action potential.

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Hille, B. (1977) Local Anesthetics: Hydrophilic and Hydrophobic Pathways for the Drug-Receptor Reaction. The Journal of General Physiology, 69, 497-515.

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Kazarinova-Noyes K, Malhotra JD, McEwen DP, Mattei LN, Berglund EO, Ranscht B, Levinson SR, Schachner M, Shrager P, Isom LL, Xiao ZC (October 2001).

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certain kinds of neurons. Mutations that interfere with Na channel inactivation can contribute to cardiovascular diseases or epileptic seizures by

612: 9652: 8273: 7018: 6963: 6958: 6923: 2698:"Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons" 9134: 8897: 8827: 7756: 7613: 7488: 7232: 7080: 7043: 6943: 6938: 6838: 6823: 6818: 6783: 17: 1259:

the cell. Thus, the more Na channels localized in a region of a cell's membrane the faster the action potential will propagate and the more

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Cardiac myocytes, uninnervated skeletal muscle, central neurons, gastrointestinal smooth muscle cells and Interstitial cells of Cajal

9154: 8476: 8125: 7222: 4294:"A Mixed Periodic Paralysis & Myotonia Mutant, P1158S, Imparts pH-Sensitivity in Skeletal Muscle Voltage-gated Sodium Channels" 9392: 7345: 6080: 6063: 6058: 6053: 6048: 428:

When the membrane's voltage becomes low enough, the inactivation gate reopens and the activation gate closes in a process called

264:, about −70 mV in most human neurons, and Na channels are in their deactivated state, blocked on the extracellular side by their 1937:"International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels" 7242: 7168: 6085: 5183: 4455: 3623:

Xie, Jiongfang; Ke, Meng; Xu, Lizhen; Lin, Shiyi; Huang, Jin; Zhang, Jiabei; Yang, Fan; Wu, Jianping; Yan, Zhen (2020-11-17).

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In addition to regulating channel gating, sodium channel beta subunits also modulate channel expression and form links to the

9687: 8177: 3932: 3446:"Extracellular calcium controls background current and neuronal excitability via an UNC79-UNC80-NALCN cation channel complex" 1752: 1719: 1677: 8617: 8595: 6691: 6137: 5318: 2940:"Sodium channel beta1 and beta3 subunits associate with neurofascin through their extracellular immunoglobulin-like domain" 1467: 9775: 8490: 6035: 5056: 2206:"Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome" 3748:"Mutations in NALCN cause an autosomal-recessive syndrome with severe hypotonia, speech impairment, and cognitive delay" 9419: 6724: 5821: 1002:

possibly inducing neurite outgrowth. Beta 3 and beta 1 bind to neurofascin at Nodes of Ranvier in developing neurons.

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Lear, Bridget C.; Lin, Jui-Ming; Keath, J. Russel; McGill, Jermaine J.; Raman, Indira M.; Allada, Ravi (2005-12-02).

2649:"Contactin associates with sodium channel Nav1.3 in native tissues and increases channel density at the cell surface" 2604:

Cantrell AR, Catterall WA (June 2001). "Neuromodulation of Na+ channels: an unexpected form of cellular plasticity".

221:, S – ion selectivity, I – inactivation. Positive (+) charges in S4 are important for transmembrane voltage sensing. 7689: 2160:

Chockalingam P, Wilde A (September 2012). "The multifaceted cardiac sodium channel and its clinical implications".

865: 861: 3257:"The Neuronal Channel NALCN Contributes Resting Sodium Permeability and Is Required for Normal Respiratory Rhythm" 2524:"Sodium channel beta subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact" 8380: 8200: 6684: 6414: 5413: 5191: 4507: 3915:

Peters CH, Ghovanloo MR, Gershome C, Ruben PC (February 2018). "pH Modulation of Voltage-Gated Sodium Channels".

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Vargas-Alarcon G, Alvarez-Leon E, Fragoso JM, Vargas A, Martinez A, Vallejo M, Martinez-Lavin M (February 2012).

982:(ECM) molecules. Contactin, also known as F3 or F11, associates with beta 1 as shown via co-immunoprecipitation. 716: 3565:"A Putative Cation Channel and Its Novel Regulator: Cross-Species Conservation of Effects on General Anesthesia" 2840:"Interaction of voltage-gated sodium channels with the extracellular matrix molecules tenascin-C and tenascin-R" 1572:

1.4 remains insensitive to acidosis. The voltage-dependence of steady-state fast inactivation is unchanged in Na

174: 6436: 1268: 30: 3805:"Genomewide association study in cervical dystonia demonstrates possible association with sodium leak channel" 1531:

which makes it the most pH-sensitive sodium channel among the sodium channels that have been studied to date.

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1.9. The gene names are referred to as SCN1A through SCN5A, then SCN8A through SCN11A. The "tenth member", Na

91: 9746: 6011: 4923: 199: 123: 2404:"From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels" 2353:"A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia" 9726: 6286: 3503:"A putative cation channel, NCA-1, and a novel protein, UNC-80, transmit neuronal activity in C. elegans" 421: 998:-like (EGF-like) repeats that repel beta2. A disintegrin and metalloproteinase (ADAM) 10 sheds beta 2's 478: 9770: 4464: 4448: 1871:

Yan, Zhen, et al. "Structure of the Nav1. 4-β1 complex from electric eel." Cell 170.3 (2017): 470-482.

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molecules. Most channels of this type are permeable to potassium to some degree as well as to sodium.

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and the DEKA motif of the voltage-gated sodium channel, possibly explaining its lack of selectivity.

803: 42: 3958:"Effects of external protons on single cardiac sodium channels from guinea pig ventricular myocytes" 3690:"The Ion Channel Narrow Abdomen Is Critical for Neural Output of the Drosophila Circadian Pacemaker" 2253:

Butler KM, da Silva C, Shafir Y, Weisfeld-Adams JD, Alexander JJ, Hegde M, Escayg A (January 2017).

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compilation of genetic variations in the SCN1A gene that alter the expression or function of Nav1.1

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Lu, Boxun; Su, Yanhua; Das, Sudipto; Wang, Haikun; Wang, Yan; Liu, Jin; Ren, Dejian (2009-02-05).

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Smith RS, Kenny CJ, Ganesh V, Jang A, Borges-Monroy R, Partlow JN, et al. (September 2018).

1985:"Structure-guided unlocking of NaX reveals a non-selective tetrodotoxin-sensitive cation channel" 995: 237: 4059:"Role of outer ring carboxylates of the rat skeletal muscle sodium channel pore in proton block" 1826:

Nicholls, Martin, Fuchs, Brown, Diamond, Weisblat. (2012) "From Neuron to Brain," 5th ed. pg. 86

9364: 9300: 8691: 7657: 7648: 7212: 7199: 7181: 7123: 6747: 6666: 4658: 4645: 4632: 4612: 4599: 4564: 1528: 1304: 1264: 1218: 911: 887: 720: 598: 465: 3386:"The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic beta-cell line" 1172: 1131: 1086: 1048: 934: 838: 792: 741: 705: 681: 646: 592: 9328: 9229: 4441: 4108:"Acidosis differentially modulates inactivation in na(v)1.2, na(v)1.4, and na(v)1.5 channels" 3197:"Cloning of a novel four repeat protein related to voltage-gated sodium and calcium channels" 1500:

to the trigger of an action potential (-55mV), thus increasing the excitability of a neuron.

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Lu, Boxun; Zhang, Qi; Wang, Haikun; Wang, Yan; Nakayama, Manabu; Ren, Dejian (2010-11-04).

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The following naturally produced substances persistently activate (open) sodium channels:

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Hermansen L, Osnes JB (March 1972). "Blood and muscle pH after maximal exercise in man".

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Lu, Boxun; Su, Yanhua; Das, Sudipto; Liu, Jin; Xia, Jingsheng; Ren, Dejian (2007-04-20).

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Malhotra JD, Koopmann MC, Kazen-Gillespie KA, Fettman N, Hortsch M, Isom LL (July 2002).

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residues, which attract the positive Na ion and keep out negatively charged ions such as

457: 449: 4309: 3640: 3332: 2855: 2565:"Structural requirements for interaction of sodium channel beta 1 subunits with ankyrin" 2465: 7983: 7978: 7881: 7588: 7358: 6006: 4882: 4529: 4375: 4350: 4326: 4293: 4234: 4209: 4185: 4158: 4134: 4107: 4083: 4058: 4034: 4009: 3982: 3957: 3897: 3837: 3804: 3780: 3747: 3727: 3665: 3624: 3602: 3537: 3502: 3478: 3445: 3418: 3385: 3357: 3316: 3294: 3232: 3082: 3049: 3018: 2993: 2964: 2939: 2815: 2806: 2790: 2771: 2722: 2697: 2673: 2648: 2629: 2433: 2379: 2352: 2328: 2303: 2279: 2254: 2230: 2205: 2185: 2137: 2110: 2009: 1984: 1964: 1914: 1687: 1248: 115: 3212: 2420: 2403: 1804: 1777: 1584:

1.5 is depolarized. Hence, among the sodium channels that have been studied so far, Na

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Shah BS, Rush AM, Liu S, Tyrrell L, Black JA, Dib-Hajj SD, Waxman SG (August 2004).

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describing transitions between states; in the latter, the channels are treated as a

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Wittmack EK, Rush AM, Craner MJ, Goldfarb M, Waxman SG, Dib-Hajj SD (July 2004).

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Isom LL (February 2001). "Sodium channel beta subunits: anything but auxiliary".

1602: 857: 711: 656: 616: 218: 4270: 2255:"De novo and inherited SCN8A epilepsy mutations detected by gene panel analysis" 2111:"V1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development" 1744: 1568:

1.5 display depolarized voltage-dependence of activation, while activation in Na

1267:. The ability of these channels to assume a closed-inactivated state causes the 9637: 9593: 9184: 9084: 8994: 8524: 8467: 8312: 8268: 8223: 7968: 7958: 7578: 7498: 7095: 6998: 6145: 4317: 4159:"Proton sensors in the pore domain of the cardiac voltage-gated sodium channel" 3763: 3648: 3273: 3256: 2844:

Proceedings of the National Academy of Sciences of the United States of America

2086: 2069: 2000: 1902: 1657: 1395: 1256: 1251:, a small but significant number of Na ions will move into the cell down their 560:

Nomenclature and some functions of voltage-gated sodium channel alpha subunits

489:. The cations flow into a more constricted part of the pore that is 0.3 by 0.5 158: 54: 7128: 6723: 3581: 3564: 1385: 1359:, e.g., grayanotoxin I (other granotoxins inactive, or close, sodium channels) 1009:

Nomenclature and some functions of voltage-gated sodium channel beta subunits

9764: 9647: 9540: 9486: 9471: 9257: 9194: 8927: 8872: 8867: 8857: 8812: 8632: 8566: 8418: 8228: 8213: 8058: 7751: 7633: 7473: 7353: 7332: 7307: 7227: 6848: 6843: 6099: 5772: 4210:"Isoform-dependent interaction of voltage-gated sodium channels with protons" 4124: 3885: 3828: 3771: 3715: 3656: 3590: 3528: 3469: 3409: 3348: 3282: 3220: 3073: 2994:"Brugada Syndrome: Clinical, Genetic, Molecular, Cellular, and Ionic Aspects" 2864: 2540: 2523: 1872: 1463: 1462:) which in turn increase the permeability of NALCN through UNC80 activation. 1356: 1335: 1226: 1031: 964: 848: 575: 214: 57: 6132: 6030: 4175: 2473: 2369: 1860: 1794: 9519: 9267: 9179: 9169: 9079: 9014: 8912: 8842: 8777: 8767: 8722: 8346: 8331: 8278: 8233: 8088: 8043: 8028: 8018: 8003: 7943: 7583: 7563: 7503: 7053: 6908: 6768: 6452: 5843: 4384: 4335: 4243: 4194: 4143: 4092: 3942: 3893: 3846: 3789: 3723: 3674: 3598: 3546: 3487: 3427: 3401: 3366: 3290: 3228: 3178: 3137: 3091: 3027: 2973: 2924: 2915: 2898: 2824: 2767: 2731: 2682: 2625: 2590: 2581: 2564: 2549: 2429: 2388: 2337: 2288: 2239: 2181: 2146: 2095: 2018: 1960: 1910: 1813: 1762: 1707: 1435: 1207: 967: 869: 518: 4278: 4043: 4025: 3991: 3973: 3919:. Handbook of Experimental Pharmacology. Vol. 246. pp. 147–160. 3625:"Structure of the human sodium leak channel NALCN in complex with FAM155A" 3119: 2955: 2883: 2481: 1848: 1836: 1282:, producing an influx of positive charge (Na) toward the beginning of the 9318: 9272: 9149: 9144: 9139: 9064: 9049: 9044: 8999: 8978: 8970: 8882: 8877: 8862: 8847: 8782: 8727: 8303: 8293: 8288: 8283: 8263: 8248: 8238: 8218: 8120: 8103: 8093: 8083: 8073: 8068: 8038: 8013: 8008: 7988: 7973: 7938: 7923: 7886: 7821: 7781: 7771: 7628: 7623: 7608: 7593: 7533: 7398: 7302: 7297: 7292: 7282: 7277: 7158: 7105: 7100: 7085: 6928: 6903: 6893: 6883: 6873: 6863: 6778: 6773: 6763: 6676: 6382: 6377: 6372: 6367: 6254: 6093: 4468: 1739:. Metal Ions in Life Sciences. Vol. 16. Springer. pp. 325–347. 1620: 1447: 1443: 1362: 983: 525:

Likely evolutionary relationship of the nine known human sodium channels.

50: 46: 4418:. International Union of Basic and Clinical Pharmacology. Archived from 3924: 3340: 456:-type formalism. In the former scheme, each channel occupies a distinct 260:

Before an action potential occurs, the axonal membrane is at its normal

9622: 9550: 9545: 9481: 9476: 9466: 9461: 9441: 9262: 9251: 9247: 9214: 9099: 9094: 9069: 9059: 9034: 9029: 9024: 8965: 8955: 8937: 8932: 8902: 8892: 8852: 8817: 8772: 8762: 8757: 8752: 8737: 8702: 8627: 8571: 8548: 8516: 8443: 8403: 8361: 8351: 8326: 8298: 8258: 8243: 8163: 8158: 8098: 8078: 8063: 8053: 7918: 7908: 7836: 7831: 7826: 7816: 7776: 7731: 7726: 7638: 7618: 7558: 7548: 7478: 7458: 7443: 7433: 7423: 7408: 7393: 7383: 7373: 7363: 7322: 7317: 7312: 7287: 7267: 7247: 7173: 7163: 7148: 7138: 7090: 7038: 6973: 6898: 6888: 6878: 6858: 6833: 6828: 6808: 6788: 6758: 6362: 5728: 5096: 5064: 3104: 2350: 2304:"Sodium channel mutations in epilepsy and other neurological disorders" 1434:

NALCN is not blocked by many common sodium channel blockers, including

1350: 1345: 1340: 999: 493:

wide, which is just large enough to allow a single Na ion with a water

482: 4157:

Jones DK, Peters CH, Allard CR, Claydon TW, Ruben PC (February 2013).

3917:

Voltage-gated Sodium Channels: Structure, Function and Channelopathies

3820: 3128: 3050:"Sodium leak channels in neuronal excitability and rhythmic behaviors" 2562: 1952: 940:

heart, uterus, skeletal muscle, astrocytes, dorsal root ganglion cells

9642: 9588: 9504: 9387: 9377: 9308: 9237: 9199: 9174: 9164: 9089: 9039: 8984: 8960: 8887: 8797: 8792: 8787: 8747: 8742: 8732: 8717: 8576: 8448: 8428: 8408: 8398: 8356: 8336: 8253: 8048: 7963: 7953: 7933: 7871: 7856: 7846: 7806: 7791: 7761: 7746: 7741: 7736: 7662: 7603: 7553: 7543: 7538: 7523: 7513: 7493: 7483: 7463: 7438: 7068: 7033: 7013: 6978: 6968: 6933: 6918: 6447: 6357: 2617: 2319: 1608: 1543: 1459: 1439: 1330: 498: 490: 4463: 2788: 2068:

Bennett DL, Clark AJ, Huang J, Waxman SG, Dib-Hajj SD (April 2019).

440:, which can cause muscle and/or nerve cells to become over-excited. 9313: 9119: 9114: 9074: 8989: 8837: 8712: 8650: 8033: 7998: 7903: 7518: 7448: 7418: 7378: 7272: 7063: 7023: 7003: 6460: 5808: 4787: 4782: 4777: 4772: 4704: 4699: 3195:

Lee, Jung-Ha; Cribbs, Leanne L.; Perez-Reyes, Edward (1999-02-26).

2937: 2897:

Kim DY, Ingano LA, Carey BW, Pettingell WH, Kovacs DM (June 2005).

1324: 991: 987: 975: 958: 817: 809: 660: 608: 494: 486: 4208:

Khan A, Kyle JW, Hanck DA, Lipkind GM, Fozzard HA (October 2006).

4057:

Khan A, Romantseva L, Lam A, Lipkind G, Fozzard HA (August 2002).

2938:

Ratcliffe CF, Westenbroek RE, Curtis R, Catterall WA (July 2001).

2521: 2252: 2025: 1655: 9382: 9204: 9004: 8529: 7928: 7866: 7528: 7508: 7204: 7075: 6587: 6344: 6180: 4681: 4676: 4671: 3151:

Possani LD, Becerril B, Delepierre M, Tytgat J (September 1999).

2522:

Malhotra JD, Kazen-Gillespie K, Hortsch M, Isom LL (April 2000).

1426: 1379: 1271:

and is critical for the propagation of action potentials down an

1065:

Central Neurons, Peripheral Neurons, skeletal muscle, heart, glia

971: 209: 3744: 9208: 8472:

Tooltip G protein-coupled inwardly rectifying potassium channel

8321: 8317:

Tooltip G protein-coupled inwardly rectifying potassium channel

7993: 7913: 7796: 7786: 7568: 7337: 6264: 6259: 5993: 5988: 5934: 5929: 5745: 5733: 5723: 5718: 5706: 5701: 5696: 5583: 5578: 5573: 5465: 5401: 5396: 5391: 5386: 5381: 5376: 5371: 5306: 5301: 5291: 5286: 5281: 5232: 5227: 5217: 5212: 5089: 5084: 5079: 5074: 4980: 4975: 4970: 4960: 4955: 4945: 4940: 4870: 4865: 4860: 4855: 4758: 4753: 4748: 4743: 4731: 4726: 4721: 4716: 4625: 4592: 4587: 4582: 4577: 3150: 1247:. If enough channels open when there is a change in the cell's 901: 877: 828: 821: 813: 731: 695: 636: 623:

or SMEI), borderline SMEI (SMEB), West syndrome (also known as

582: 531: 166: 162: 132: 4292:

Ghovanloo MR, Abdelsayed M, Peters CH, Ruben PC (April 2018).

4291: 9688: 8178: 7948: 7801: 6498: 6429: 6424: 6419: 6336: 6323: 6318: 6313: 6308: 6303: 6298: 6249: 6242: 6237: 6232: 6227: 6222: 6217: 6212: 6207: 6195: 6190: 6185: 6175: 6170: 6165: 6160: 6075: 6019: 5976: 5971: 5966: 5961: 5956: 5951: 5946: 5924: 5919: 5914: 5909: 5904: 5899: 5894: 5875: 5870: 5865: 5860: 5848: 5765: 5760: 5755: 5740: 5678: 5673: 5668: 5659: 5654: 5640: 5635: 5626: 5621: 5616: 5607: 5602: 5593: 5588: 5555: 5550: 5545: 5540: 5531: 5522: 5517: 5512: 5503: 5498: 5493: 5488: 5479: 5474: 5460: 5455: 5450: 5445: 5440: 5435: 5430: 5366: 5361: 5356: 5351: 5346: 5341: 5336: 5331: 5296: 5266: 5261: 5256: 5251: 5222: 5171: 5166: 5161: 5156: 5146: 5141: 5121: 5106: 5101: 5016: 5011: 5006: 5001: 4985: 4965: 4950: 4911: 4906: 4901: 4896: 4804: 4799: 4522: 4517: 4512: 3382: 2070:"The Role of Voltage-Gated Sodium Channels in Pain Signaling" 1162: 1121: 1076: 1038: 925: 782: 671: 213:

Diagram of a voltage-sensitive sodium channel α-subunit. G –

8596: 3914: 3860:

Wang, Ke-Sheng; Liu, Xue-Feng; Aragam, Nagesh (2010-12-01).

3802: 2837: 9524:

Tooltip Cystic fibrosis transmembrane conductance regulator

9446: 8491: 8149: 8111: 7894: 6578: 6573: 6568: 6558: 6553: 6548: 6538: 6533: 6528: 6523: 6518: 6513: 6508: 6493: 6488: 6483: 6478: 6473: 6468: 6407: 6402: 6397: 6392: 6387: 6293: 6281: 6276: 6271: 6202: 6155: 6119: 6114: 6109: 6104: 5831: 5649: 5207: 4544: 4534: 4008:

Sun YM, Favre I, Schild L, Moczydlowski E (December 1997).

3562: 1605: – Ion channel complex through which calcium ions pass 1430:

Regulatory pathways and chemicals affecting NALCN function.

1375:

The following toxins modify the gating of sodium channels:

1272: 170: 9420: 6725: 4007: 2695: 1981: 1714:(3rd ed.). Sunderland, Mass: Sinauer. pp. 73–7. 1152:

central neurons, adrenal gland, kidney, peripheral neurons

5151: 5111: 2838:

Srinivasan J, Schachner M, Catterall WA (December 1998).

2202: 2033: 1534: 448:

The temporal behavior of Na channels can be modeled by a

7690: 4156: 4056: 2896: 2744: 1548:

The effects of protonation have been characterized in Na

1413: 1243:

Voltage-gated sodium channels play an important role in

687:

Central neurons, peripheral neurons and cardiac myocytes

8381: 8201: 2450: 2067: 1631:

Pages displaying short descriptions of redirect targets

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that area of the cell will be. This is an example of a

1193:

heart, skeletal muscle, central and peripheral neurons

8678: 2991: 1934: 1778:"Overview of the voltage-gated sodium channel family" 27:

Transmembrane protein allowing sodium ions in and out

4348: 4207: 3194: 2108: 1935:

Catterall WA, Goldin AL, Waxman SG (December 2005).

4349:Ghovanloo MR, Peters CH, Ruben PC (October 2018). 3687: 3500: 2646: 1661: 1544:pH modulation across the subtypes studied thus far 1438:. NALCN is blocked nonspecifically by both Gd and 1278:Na channels both open and close more quickly than 9713: 9287: 2603: 2159: 1487:the axon, and contributes to membrane stability. 443: 9762: 9351: 6621: 4105: 1700: 1668:(4th ed.). New York: McGraw-Hill. pp. 1649: 1111:Central Neurons, peripheral neurons, heart, glia 959:Role of beta subunits as cell adhesion molecules 229:that associate with accessory proteins, such as 193: 9751:Transient receptor potential channel modulators 3955: 3443: 1202: 472: 4256: 4003: 4001: 2301: 1404: 1210:sodium channels are activated by binding of a 866:channelopathy-associated insensitivity to pain 9693:Tooltip Transient receptor potential channels 8183:Tooltip Inwardly rectifying potassium channel 6692: 4449: 4416:IUPHAR Database of Receptors and Ion Channels 3859: 3098: 1706: 1580:1.4, but steady-state fast inactivation in Na 8601:Tooltip Tandem pore domain potassium channel 4285: 4201: 4150: 4099: 4050: 3908: 3144: 2992:Antzelevitch C, Patocskai B (January 2016). 2931: 2890: 2782: 2738: 2689: 2640: 2597: 2556: 2515: 2395: 2344: 2196: 1930: 1928: 1692:: CS1 maint: multiple names: authors list ( 868:and recently discovered a disabling form of 8499:Tooltip Calcium-activated potassium channel 4250: 3998: 3949: 3314: 3153:"Scorpion toxins specific for Na+-channels" 2831: 2444: 1775: 1592:1.5 is the most proton-sensitive subtypes. 1293: 1232: 1214:instead of a change in membrane potential. 537:The proteins of these channels are named Na 9425:Tooltip Calcium-activated chloride channel 7717:4-Aminopyridine (fampridine/dalfampridine) 6730:Tooltip Voltage-dependent calcium channels 6706: 6699: 6685: 4456: 4442: 3622: 3254: 1873:https://doi.org/10.1016/j.cell.2017.06.039 173:, sodium channels are responsible for the 5040: 4485: 4403:at the U.S. National Library of Medicine 4374: 4325: 4233: 4184: 4174: 4133: 4123: 4082: 4033: 3981: 3956:Zhang JF, Siegelbaum SA (December 1991). 3836: 3779: 3705: 3664: 3580: 3536: 3518: 3477: 3417: 3356: 3272: 3168: 3127: 3081: 3017: 2963: 2914: 2873: 2863: 2814: 2721: 2672: 2580: 2539: 2419: 2401: 2378: 2368: 2327: 2278: 2229: 2136: 2126: 2085: 2008: 1925: 1861:https://doi.org/10.1016/j.bpj.2021.12.025 1803: 1793: 1737:The Alkali Metal Ions: Their Role in Life 1466:can also increase NALCN activity through 118:, which is also called change in voltage 7695:Tooltip Voltage-gated potassium channels 1734: 1425: 517: 208: 29: 8389:Tooltip ATP-sensitive potassium channel 8209:Tooltip ATP-sensitive potassium channel 6609: 4828: 1975: 1884: 1882: 1880: 1849:https://doi.org/10.1073/pnas.1814928115 994:-R bind with beta 2 in contrast to the 477:The pore of sodium channels contains a 14: 9763: 4106:Vilin YY, Peters CH, Ruben PC (2012). 2302:Meisler MH, Kearney JA (August 2005). 1837:http://dx.doi.org/10.1085/jgp.69.4.497 1535:pH modulation of sodium channel gating 1490: 760:progressive cardiac conduction disease 8683:Tooltip Voltage-gated sodium channels 6680: 6608: 5793: 5039: 4827: 4484: 4437: 3618: 3616: 3558: 3556: 3439: 3437: 3378: 3376: 3310: 3308: 3250: 3248: 3246: 3190: 3188: 3043: 3041: 3039: 3037: 2987: 2985: 2983: 2308:The Journal of Clinical Investigation 2063: 2061: 2059: 2057: 1623: – Pore-forming membrane protein 1414:Structural and functional differences 86:(factor that stimulates the channel) 8618:12-O-Tetradecanoylphorbol-13-acetate 2748:The European Journal of Neuroscience 2031: 1888: 1877: 1522:Molecular mechanisms of proton block 1503: 690:epilepsy, pain, brain malformations 7712:3,4-Diaminopyridine (amifampridine) 5822:Calcium-activated chloride channels 4163:The Journal of Biological Chemistry 3108:The Journal of Experimental Biology 3047: 2903:The Journal of Biological Chemistry 2569:The Journal of Biological Chemistry 2528:The Journal of Biological Chemistry 1712:Ion Channels of Excitable Membranes 1629: – Class of transport proteins 1370: 652:Central neurons, peripheral neurons 621:severe myclonic epilepsy of infancy 226: 24: 4892:Amiloride-sensitive cation channel 3752:American Journal of Human Genetics 3613: 3553: 3434: 3373: 3305: 3243: 3185: 3034: 2980: 2807:10.1523/JNEUROSCI.21-19-07517.2001 2054: 1638: – Use of sodium by organisms 1617: – Group of membrane proteins 1481: 1472:muscarinic acetylcholine receptors 1286:and an efflux (K) toward the end. 230: 72:They are classified into 2 types: 25: 9792: 9718:Tooltip Ligand gated ion channels 9292:Tooltip Epithelial sodium channel 5794: 4394: 4014:The Journal of General Physiology 3962:The Journal of General Physiology 1769: 896:pain, neuropsychiatric disorders 627:), Doose syndrome (also known as 553:is summarized in table 1, below. 513: 225:Sodium channels consist of large 67: 9356:Tooltip Acid-sensing ion channel 3170:10.1046/j.1432-1327.1999.00625.x 3157:European Journal of Biochemistry 2760:10.1111/j.1460-9568.2006.04789.x 2271:10.1016/j.eplepsyres.2016.11.002 1611: – Electrophysiology metric 1512: 949: 6415:Voltage-dependent anion channel 4508:Inositol trisphosphate receptor 4412:"Voltage-Gated Sodium Channels" 4342: 3853: 3796: 3738: 3681: 3494: 3010:10.1016/j.cpcardiol.2015.06.002 2496:"Blackboard Server Unavailable" 2488: 2295: 2246: 2153: 2102: 2040:from the original on 2011-07-21 717:hyperkalemic periodic paralysis 7174:Ziconotide (ω-conotoxin MVIIA) 6437:General bacterial porin family 2998:Current Problems in Cardiology 2714:10.1523/JNEUROSCI.1628-04.2004 2665:10.1523/JNEUROSCI.0322-04.2004 1865: 1853: 1841: 1829: 1820: 1728: 501:residues that line the pore. 444:Modeling the behavior of gates 194:Voltage-gated sodium channels 184: 131:binding of substances such as 62:superfamily of cation channels 13: 1: 9747:Receptor/signaling modulators 7149:Leconotide (ω-conotoxin CVID) 4367:10.1080/19336950.2018.1539611 4259:Journal of Applied Physiology 3213:10.1016/S0014-5793(99)00082-4 2421:10.1016/S0896-6273(00)81133-2 2357:BMC Musculoskeletal Disorders 1643: 1556:1.5. Among these channels, Na 1421:voltage-gated calcium channel 1309: 1203:Ligand-gated sodium channels 725:potassium-aggravated myotonia 396:Repolarized → Hyperpolarized 92:Voltage-gated sodium channels 18:Voltage-gated sodium channels 4226:10.1113/jphysiol.2006.115659 4075:10.1113/jphysiol.2002.021014 3878:10.1016/j.schres.2010.09.002 3707:10.1016/j.neuron.2005.10.030 3520:10.1371/journal.pbio.0060055 3462:10.1016/j.neuron.2010.09.014 3066:10.1016/j.neuron.2011.12.007 2606:Nature Reviews. Neuroscience 2222:10.1053/j.gastro.2014.02.054 2174:10.1136/heartjnl-2012-301784 2128:10.1016/j.neuron.2018.07.052 1776:Yu FH, Catterall WA (2003). 1664:Principles of Neural Science 1458:(independent of the coupled 1217:They are found, e.g. in the 504: 473:Impermeability to other ions 204: 200:voltage-gated sodium channel 124:ligand-gated sodium channels 7: 4271:10.1152/jappl.1972.32.3.304 2944:The Journal of Cell Biology 2795:The Journal of Neuroscience 2702:The Journal of Neuroscience 2653:The Journal of Neuroscience 2402:Catterall WA (April 2000). 1745:10.1007/978-3-319-21756-7_9 1595: 1405:Sodium leak channel (NALCN) 1298: 986:-like (FN-like) repeats of 481:made of negatively charged 413:Hyperpolarized → Polarized 152: 10: 9797: 9776:Integral membrane proteins 8710:Antiarrhythmics (class I): 5856:Chloride Channel Accessory 4465:Membrane transport protein 4318:10.1038/s41598-018-24719-y 3764:10.1016/j.ajhg.2013.08.001 3649:10.1038/s41467-020-19667-z 3274:10.1016/j.cell.2007.02.041 3048:Ren, Dejian (2011-12-22). 2087:10.1152/physrev.00052.2017 2001:10.1038/s41467-022-28984-4 1903:10.1177/107385840100700108 1497:resting membrane potential 1313: 1302: 1236: 629:myoclonic astatic epilepsy 362:Depolarized → Repolarized 197: 43:integral membrane proteins 9740: 9711: 9686: 9679: 9613: 9606: 9559: 9531: 9517: 9495: 9432: 9418: 9409: 9363: 9349: 9327: 9299: 9285: 9228: 9220:Tricyclic antidepressants 8690: 8676: 8667: 8641: 8608: 8594: 8538: 8506: 8489: 8370: 8229:Glibenclamide (glyburide) 8190: 8176: 8139: 7702: 7688: 7679: 7647: 6737: 6714: 6662: 6617: 6604: 6445: 6334: 6130: 6028: 6004: 5806: 5802: 5789: 5412: 5317: 5182: 5055: 5051: 5035: 4922: 4881: 4851:Epithelial sodium channel 4843: 4839: 4823: 4555: 4500: 4496: 4480: 4214:The Journal of Physiology 4112:Frontiers in Pharmacology 4063:The Journal of Physiology 3582:10.1016/j.cub.2007.02.037 1615:Epithelial sodium channel 1454:through their respective 1290:excitability) of a cell. 872:(rs6754031 polymorphism) 393:Inactivated → Deactivated 251: 4768:Cation channels of sperm 4405:Medical Subject Headings 4125:10.3389/fphar.2012.00109 2865:10.1073/pnas.95.26.15753 2541:10.1074/jbc.275.15.11383 2204:Farrugia G (June 2014). 1294:Pharmacologic modulation 1253:electrochemical gradient 1233:Role in action potential 1225:, where the ligands are 774:Irritable bowel syndrome 768:ventricular fibrillation 665:autism spectrum disorder 328:Polarized → Depolarized 34:C is the sodium channel 8833:Eslicarbazepine acetate 4176:10.1074/jbc.M112.434266 2474:10.1126/science.1375395 2370:10.1186/1471-2474-13-23 1941:Pharmacological Reviews 1795:10.1186/gb-2003-4-3-207 1588:1.4 is the least and Na 996:Epidermal growth factor 847:, sympathetic neurons, 342:Activated → Inactivated 308:Deactivated → Activated 169:, and certain types of 8577:Rottlerin (mallotoxin) 6708:Ion channel modulators 3866:Schizophrenia Research 3402:10.1038/embor.2009.125 2916:10.1074/jbc.M412938200 2582:10.1074/jbc.M202354200 1660:, Schwartz JH (2000). 1529:cardiac sodium channel 1478:which inhibits UNC80. 1431: 1305:Sodium channel blocker 1265:positive feedback loop 1219:neuromuscular junction 721:paramyotonia congenita 526: 462:differential equations 294:Neuron's Target State 222: 78:Type of sodium channel 35: 6934:Ryodipine (riodipine) 4844:Constitutively active 4026:10.1085/jgp.110.6.693 3974:10.1085/jgp.98.6.1065 3629:Nature Communications 3120:10.1242/jeb.204.4.711 2956:10.1083/jcb.200102086 2074:Physiological Reviews 1989:Nature Communications 1429: 1316:Sodium channel opener 521: 242:transmembrane voltage 212: 146:Ungated, always open 60:. They belong to the 33: 8923:Valproate semisodium 7454:Carboxyamidotriazole 7389:Gabapentin enacarbil 7369:Arbaclofen placarbil 980:extracellular matrix 853:neuroendocrine cells 140:Leak sodium channel 9574:1,10-Phenanthroline 8131:Spooky toxin (SsTx) 7116:Tetrahydropalmatine 6611:By gating mechanism 4310:2018NatSR...8.6304G 3925:10.1007/164_2018_99 3641:2020NatCo..11.5831X 3341:10.1038/nature07579 3333:2009Natur.457..741L 2856:1998PNAS...9515753S 2466:1992Sci...256..839I 1627:Resting ion channel 1491:Biological function 1223:nicotinic receptors 1010: 917:Dorsal root ganglia 893:Dorsal root ganglia 845:Dorsal root ganglia 806:, heart, glia cells 800:dorsal root ganglia 764:atrial fibrillation 561: 291:Gate's Target State 105:"voltage-sensitive" 102:"voltage-dependent" 9584:7,8-Benzoquinoline 9579:4,7-Phenanthroline 9569:1,7-Phenanthroline 8945:Local anesthetics: 8477:ML-297 (VU0456810) 7984:Diallyl trisulfide 7979:Dextropropoxyphene 7882:Tetraethylammonium 7589:Pinaverium bromide 7359:4-Methylpregabalin 6138:TRP cation channel 6036:CNG cation channel 5319:Tandem pore domain 4530:Ryanodine receptor 4298:Scientific Reports 3809:Movement Disorders 2503:blackboard.jhu.edu 1891:The Neuroscientist 1452:Src family kinases 1432: 1249:membrane potential 1068:epilepsy (GEFS+), 1027:Expression profile 1005: 804:peripheral neurons 772:Gastrointestinal: 571:Expression profile 556: 527: 479:selectivity filter 422:inactivation gates 285:Membrane Potential 223: 116:membrane potential 36: 9771:Electrophysiology 9758: 9757: 9736: 9735: 9675: 9674: 9671: 9670: 9633:Meclofenamic acid 9602: 9601: 9513: 9512: 9405: 9404: 9401: 9400: 9345: 9344: 9281: 9280: 9155:RG7893 (GDC-0287) 8918:Valproate pivoxil 8808:Acetylpheneturide 8663: 8662: 8659: 8658: 8590: 8589: 8562:Meclofenamic acid 8525:Ethanol (alcohol) 8485: 8484: 8434:Minoxidil sulfate 8172: 8171: 7675: 7674: 7671: 7670: 7574:Otilonium bromide 7499:Ethanol (alcohol) 7263:ω-Conotoxin MVIIC 6999:Phenylalkylamines 6674: 6673: 6658: 6657: 6654: 6653: 6646:Stretch-activated 6623:Ion channel class 6600: 6599: 6596: 6595: 5785: 5784: 5781: 5780: 5057:Calcium-activated 5045:Potassium channel 5031: 5030: 5027: 5026: 4819: 4818: 4815: 4814: 4220:(Pt 2): 493–501. 3934:978-3-319-90283-8 3821:10.1002/mds.25732 3327:(7230): 741–744. 2259:Epilepsy Research 2121:(5): 905–913.e7. 1953:10.1124/pr.57.4.4 1754:978-3-319-21755-0 1721:978-0-87893-321-1 1679:978-0-8385-7701-1 1636:Sodium in biology 1504:Role in pathology 1269:refractory period 1245:action potentials 1200: 1199: 1030:Associated human 947: 946: 798:Central neurons, 574:Associated human 469:Markovian model. 452:scheme or by the 417: 416: 262:resting potential 179:action potentials 150: 149: 16:(Redirected from 9788: 9719: 9715: 9694: 9690: 9684: 9683: 9611: 9610: 9529: 9528: 9525: 9521: 9430: 9429: 9426: 9422: 9416: 9415: 9361: 9360: 9357: 9353: 9297: 9296: 9293: 9289: 8908:Sodium valproate 8823:Chlorphenacemide 8805:Anticonvulsants: 8688: 8687: 8684: 8680: 8674: 8673: 8623:Arachidonic acid 8606: 8605: 8602: 8598: 8504: 8503: 8500: 8496: 8473: 8469: 8390: 8386: 8342:Dextromethorphan 8318: 8314: 8210: 8206: 8188: 8187: 8184: 8180: 7700: 7699: 7696: 7692: 7686: 7685: 7658:L-type-selective 7469:Dimeditiapramine 7431:Others/unsorted: 7213:T-type-selective 7200:R-type-selective 7182:P-type-selective 7134:ω-Conotoxin GVIA 7124:N-type-selective 6754:Dihydropyridines 6748:L-type-selective 6735: 6734: 6731: 6727: 6721: 6720: 6701: 6694: 6687: 6678: 6677: 6619: 6618: 6606: 6605: 5814:Chloride channel 5804: 5803: 5791: 5790: 5184:Inward-rectifier 5053: 5052: 5037: 5036: 4841: 4840: 4825: 4824: 4795:Two-pore channel 4498: 4497: 4482: 4481: 4458: 4451: 4444: 4435: 4434: 4430: 4428: 4427: 4389: 4388: 4378: 4346: 4340: 4339: 4329: 4289: 4283: 4282: 4254: 4248: 4247: 4237: 4205: 4199: 4198: 4188: 4178: 4154: 4148: 4147: 4137: 4127: 4103: 4097: 4096: 4086: 4054: 4048: 4047: 4037: 4005: 3996: 3995: 3985: 3953: 3947: 3946: 3912: 3906: 3905: 3857: 3851: 3850: 3840: 3800: 3794: 3793: 3783: 3742: 3736: 3735: 3709: 3685: 3679: 3678: 3668: 3620: 3611: 3610: 3584: 3560: 3551: 3550: 3540: 3522: 3498: 3492: 3491: 3481: 3441: 3432: 3431: 3421: 3380: 3371: 3370: 3360: 3312: 3303: 3302: 3276: 3252: 3241: 3240: 3207:(2–3): 231–236. 3192: 3183: 3182: 3172: 3148: 3142: 3141: 3131: 3114:(Pt 4): 711–21. 3102: 3096: 3095: 3085: 3045: 3032: 3031: 3021: 2989: 2978: 2977: 2967: 2935: 2929: 2928: 2918: 2909:(24): 23251–61. 2894: 2888: 2887: 2877: 2867: 2835: 2829: 2828: 2818: 2786: 2780: 2779: 2742: 2736: 2735: 2725: 2693: 2687: 2686: 2676: 2644: 2638: 2637: 2618:10.1038/35077553 2601: 2595: 2594: 2584: 2560: 2554: 2553: 2543: 2519: 2513: 2512: 2510: 2509: 2500: 2492: 2486: 2485: 2460:(5058): 839–42. 2448: 2442: 2441: 2423: 2399: 2393: 2392: 2382: 2372: 2348: 2342: 2341: 2331: 2320:10.1172/JCI25466 2299: 2293: 2292: 2282: 2250: 2244: 2243: 2233: 2216:(7): 1659–1668. 2210:Gastroenterology 2200: 2194: 2193: 2157: 2151: 2150: 2140: 2130: 2106: 2100: 2099: 2089: 2080:(2): 1079–1151. 2065: 2052: 2051: 2046: 2045: 2034:"SCN1A infobase" 2029: 2023: 2022: 2012: 1979: 1973: 1972: 1932: 1923: 1922: 1886: 1875: 1869: 1863: 1857: 1851: 1845: 1839: 1833: 1827: 1824: 1818: 1817: 1807: 1797: 1773: 1767: 1766: 1732: 1726: 1725: 1704: 1698: 1697: 1691: 1683: 1667: 1653: 1632: 1371:Gating modifiers 1284:action potential 1239:Action potential 1156:Brugada syndrome 1115:Brugada syndrome 1070:Brugada syndrome 1011: 1004: 756:Brugada syndrome 752:Long QT syndrome 657:febrile seizures 625:infantile spasms 603:cardiac myocytes 562: 555: 288:Target Potential 282:Action Potential 279: 278: 266:activation gates 75: 74: 21: 9796: 9795: 9791: 9790: 9789: 9787: 9786: 9785: 9781:Sodium channels 9761: 9760: 9759: 9754: 9732: 9717: 9707: 9692: 9667: 9663:Trifluoperazine 9658:Tolfenamic acid 9628:Flufenamic acid 9598: 9555: 9523: 9509: 9491: 9457:Flufenamic acid 9452:Ethacrynic acid 9424: 9397: 9355: 9341: 9323: 9291: 9277: 9224: 9055:Metabutoxycaine 9020:Diphenhydramine 9010:Cyclomethycaine 8975:Levobupivacaine 8682: 8655: 8637: 8600: 8586: 8582:Tolfenamic acid 8557:Flufenamic acid 8552: 8534: 8520: 8498: 8495: 8481: 8471: 8388: 8385: 8366: 8316: 8208: 8205: 8182: 8168: 8153: 8135: 8115: 8024:Norpropoxyphene 7901:11.1)-specific: 7900: 7694: 7667: 7643: 7599:Rhynchophylline 7349: 6729: 6710: 6705: 6675: 6670: 6650: 6613: 6592: 6441: 6340: 6330: 6126: 6024: 6000: 5798: 5777: 5691: 5568: 5425: 5408: 5313: 5277: 5247: 5203: 5195: 5178: 5132: 5047: 5023: 4996: 4935: 4918: 4877: 4835: 4811: 4694: 4666: 4653: 4640: 4620: 4607: 4572: 4551: 4492: 4490:Calcium channel 4476: 4462: 4425: 4423: 4410: 4401:Sodium+Channels 4397: 4392: 4347: 4343: 4290: 4286: 4255: 4251: 4206: 4202: 4155: 4151: 4104: 4100: 4069:(Pt 1): 71–84. 4055: 4051: 4006: 3999: 3954: 3950: 3935: 3913: 3909: 3858: 3854: 3801: 3797: 3743: 3739: 3686: 3682: 3621: 3614: 3569:Current Biology 3561: 3554: 3499: 3495: 3442: 3435: 3381: 3374: 3313: 3306: 3253: 3244: 3193: 3186: 3149: 3145: 3103: 3099: 3046: 3035: 2990: 2981: 2936: 2932: 2895: 2891: 2850:(26): 15753–7. 2836: 2832: 2801:(19): 7517–25. 2787: 2783: 2754:(10): 2551–62. 2743: 2739: 2708:(30): 6765–75. 2694: 2690: 2659:(33): 7387–99. 2645: 2641: 2602: 2598: 2575:(29): 26681–8. 2561: 2557: 2534:(15): 11383–8. 2520: 2516: 2507: 2505: 2498: 2494: 2493: 2489: 2449: 2445: 2400: 2396: 2349: 2345: 2300: 2296: 2251: 2247: 2201: 2197: 2168:(17): 1318–24. 2158: 2154: 2107: 2103: 2066: 2055: 2043: 2041: 2030: 2026: 1980: 1976: 1933: 1926: 1887: 1878: 1870: 1866: 1858: 1854: 1846: 1842: 1834: 1830: 1825: 1821: 1774: 1770: 1755: 1733: 1729: 1722: 1705: 1701: 1685: 1684: 1680: 1654: 1650: 1646: 1641: 1630: 1603:Calcium channel 1598: 1591: 1587: 1583: 1579: 1575: 1571: 1567: 1563: 1559: 1555: 1551: 1546: 1537: 1524: 1515: 1506: 1493: 1484: 1482:Protein Complex 1471: 1416: 1407: 1373: 1318: 1312: 1307: 1301: 1296: 1241: 1235: 1205: 1189: 1185: 1181: 1166: 1148: 1144: 1140: 1125: 1107: 1103: 1099: 1095: 1080: 1061: 1057: 1042: 1032:channelopathies 961: 952: 929: 905: 881: 858:erythromelalgia 832: 786: 766:and idiopathic 735: 712:Skeletal muscle 699: 675: 640: 619:(also known as 617:Dravet syndrome 599:Central neurons 586: 576:channelopathies 548: 544: 540: 516: 507: 475: 446: 438:window currents 254: 219:phosphorylation 207: 202: 196: 187: 159:excitable cells 155: 135:to the channel 111: 85: 70: 53:(Na) through a 39:Sodium channels 28: 23: 22: 15: 12: 11: 5: 9794: 9784: 9783: 9778: 9773: 9756: 9755: 9741: 9738: 9737: 9734: 9733: 9731: 9730: 9722: 9720: 9709: 9708: 9706: 9705: 9697: 9695: 9681: 9677: 9676: 9673: 9672: 9669: 9668: 9666: 9665: 9660: 9655: 9650: 9645: 9640: 9638:Mefenamic acid 9635: 9630: 9625: 9619: 9617: 9608: 9604: 9603: 9600: 9599: 9597: 9596: 9594:Phenanthridine 9591: 9586: 9581: 9576: 9571: 9565: 9563: 9557: 9556: 9554: 9553: 9548: 9543: 9537: 9535: 9526: 9515: 9514: 9511: 9510: 9508: 9507: 9501: 9499: 9493: 9492: 9490: 9489: 9484: 9479: 9474: 9469: 9464: 9459: 9454: 9449: 9444: 9438: 9436: 9427: 9413: 9407: 9406: 9403: 9402: 9399: 9398: 9396: 9395: 9390: 9385: 9380: 9375: 9369: 9367: 9358: 9347: 9346: 9343: 9342: 9340: 9339: 9333: 9331: 9325: 9324: 9322: 9321: 9316: 9311: 9305: 9303: 9294: 9283: 9282: 9279: 9278: 9276: 9275: 9270: 9265: 9260: 9255: 9242:Atracotoxins ( 9240: 9234: 9232: 9226: 9225: 9223: 9222: 9217: 9212: 9202: 9197: 9188: 9187: 9185:Zetekitoxin AB 9182: 9177: 9172: 9167: 9158: 9157: 9152: 9147: 9142: 9137: 9132: 9127: 9122: 9117: 9112: 9103: 9102: 9097: 9092: 9087: 9085:Proxymetacaine 9082: 9077: 9072: 9067: 9062: 9057: 9052: 9047: 9042: 9037: 9032: 9027: 9022: 9017: 9012: 9007: 9002: 8997: 8995:Chloroprocaine 8992: 8987: 8982: 8968: 8963: 8958: 8953: 8941: 8940: 8935: 8930: 8925: 8920: 8915: 8910: 8905: 8900: 8895: 8890: 8885: 8880: 8875: 8870: 8865: 8860: 8855: 8850: 8845: 8840: 8835: 8830: 8825: 8820: 8815: 8810: 8801: 8800: 8795: 8790: 8785: 8780: 8775: 8770: 8765: 8760: 8755: 8750: 8745: 8740: 8735: 8730: 8725: 8720: 8715: 8706: 8705: 8696: 8694: 8685: 8671: 8665: 8664: 8661: 8660: 8657: 8656: 8654: 8653: 8647: 8645: 8639: 8638: 8636: 8635: 8630: 8625: 8620: 8614: 8612: 8603: 8592: 8591: 8588: 8587: 8585: 8584: 8579: 8574: 8569: 8564: 8559: 8550: 8544: 8542: 8536: 8535: 8533: 8532: 8527: 8518: 8512: 8510: 8501: 8493: 8487: 8486: 8483: 8482: 8480: 8479: 8462: 8461: 8456: 8451: 8446: 8441: 8436: 8431: 8426: 8421: 8416: 8411: 8406: 8401: 8396: 8383: 8376: 8374: 8368: 8367: 8365: 8364: 8359: 8354: 8349: 8344: 8339: 8334: 8329: 8324: 8307: 8306: 8301: 8296: 8291: 8286: 8281: 8276: 8271: 8269:Glyclopyramide 8266: 8261: 8256: 8251: 8246: 8241: 8236: 8231: 8226: 8224:Chlorpropamide 8221: 8216: 8203: 8196: 8194: 8185: 8174: 8173: 8170: 8169: 8167: 8166: 8161: 8151: 8145: 8143: 8137: 8136: 8134: 8133: 8128: 8123: 8113: 8107: 8106: 8101: 8096: 8091: 8086: 8081: 8076: 8071: 8066: 8061: 8056: 8051: 8046: 8041: 8036: 8031: 8026: 8021: 8016: 8011: 8006: 8001: 7996: 7991: 7986: 7981: 7976: 7971: 7969:Clarithromycin 7966: 7961: 7959:Chlorpromazine 7956: 7951: 7946: 7941: 7936: 7931: 7926: 7921: 7916: 7911: 7906: 7898: 7890: 7889: 7884: 7879: 7874: 7869: 7864: 7859: 7854: 7849: 7844: 7839: 7834: 7829: 7824: 7819: 7814: 7809: 7804: 7799: 7794: 7789: 7784: 7779: 7774: 7769: 7764: 7759: 7754: 7749: 7744: 7739: 7734: 7729: 7724: 7719: 7714: 7708: 7706: 7697: 7683: 7677: 7676: 7673: 7672: 7669: 7668: 7666: 7665: 7653: 7651: 7645: 7644: 7642: 7641: 7636: 7631: 7626: 7621: 7616: 7611: 7606: 7601: 7596: 7591: 7586: 7581: 7579:Paramethadione 7576: 7571: 7566: 7561: 7556: 7551: 7546: 7541: 7536: 7531: 7526: 7521: 7516: 7511: 7506: 7501: 7496: 7491: 7486: 7481: 7476: 7471: 7466: 7461: 7456: 7451: 7446: 7441: 7436: 7427: 7426: 7421: 7416: 7411: 7406: 7401: 7396: 7391: 7386: 7381: 7376: 7371: 7366: 7361: 7354:gabapentinoids 7347: 7341: 7340: 7335: 7330: 7325: 7320: 7315: 7310: 7305: 7300: 7295: 7290: 7285: 7280: 7275: 7270: 7265: 7260: 7255:Non-selective: 7251: 7250: 7245: 7240: 7235: 7230: 7225: 7220: 7208: 7207: 7195: 7194: 7192:ω-Agatoxin IVB 7189: 7187:ω-Agatoxin IVA 7177: 7176: 7171: 7166: 7161: 7156: 7151: 7146: 7144:Huwentoxin XVI 7141: 7136: 7131: 7119: 7118: 7113: 7108: 7103: 7098: 7096:Cyproheptadine 7093: 7088: 7083: 7078: 7066: 7061: 7056: 7051: 7046: 7041: 7036: 7031: 7026: 7021: 7016: 7011: 7006: 6991: 6986: 6981: 6976: 6961: 6956: 6951: 6946: 6941: 6936: 6931: 6926: 6921: 6916: 6911: 6906: 6901: 6896: 6891: 6886: 6881: 6876: 6871: 6866: 6861: 6856: 6854:Levniguldipine 6851: 6846: 6841: 6836: 6831: 6826: 6821: 6816: 6811: 6806: 6801: 6796: 6794:Dexniguldipine 6791: 6786: 6781: 6776: 6771: 6766: 6761: 6743: 6741: 6732: 6718: 6712: 6711: 6704: 6703: 6696: 6689: 6681: 6672: 6671: 6663: 6660: 6659: 6656: 6655: 6652: 6651: 6649: 6648: 6643: 6638: 6633: 6627: 6625: 6615: 6614: 6602: 6601: 6598: 6597: 6594: 6593: 6591: 6590: 6585: 6584: 6583: 6582: 6581: 6576: 6571: 6563: 6562: 6561: 6556: 6551: 6543: 6542: 6541: 6536: 6531: 6526: 6521: 6516: 6511: 6503: 6502: 6501: 6496: 6491: 6486: 6481: 6476: 6471: 6457: 6455: 6443: 6442: 6440: 6439: 6434: 6433: 6432: 6427: 6422: 6412: 6411: 6410: 6405: 6400: 6395: 6390: 6385: 6380: 6375: 6370: 6365: 6354: 6352: 6338: 6332: 6331: 6329: 6328: 6327: 6326: 6321: 6316: 6311: 6306: 6301: 6291: 6290: 6289: 6284: 6274: 6269: 6268: 6267: 6262: 6257: 6247: 6246: 6245: 6240: 6235: 6230: 6225: 6220: 6215: 6210: 6200: 6199: 6198: 6193: 6188: 6183: 6178: 6173: 6168: 6163: 6153: 6142: 6140: 6128: 6127: 6125: 6124: 6123: 6122: 6117: 6112: 6107: 6102: 6090: 6089: 6088: 6083: 6078: 6068: 6067: 6066: 6061: 6056: 6051: 6040: 6038: 6026: 6025: 6023: 6022: 6016: 6014: 6012:Proton channel 6002: 6001: 5999: 5998: 5997: 5996: 5991: 5981: 5980: 5979: 5974: 5969: 5964: 5959: 5954: 5949: 5939: 5938: 5937: 5932: 5927: 5922: 5917: 5912: 5907: 5902: 5897: 5887: 5882: 5881: 5880: 5879: 5878: 5873: 5868: 5863: 5853: 5852: 5851: 5846: 5836: 5835: 5834: 5818: 5816: 5800: 5799: 5787: 5786: 5783: 5782: 5779: 5778: 5776: 5775: 5770: 5769: 5768: 5763: 5758: 5748: 5743: 5738: 5737: 5736: 5731: 5726: 5721: 5711: 5710: 5709: 5704: 5699: 5689: 5684: 5683: 5682: 5681: 5676: 5671: 5664: 5663: 5662: 5657: 5652: 5645: 5644: 5643: 5638: 5631: 5630: 5629: 5624: 5619: 5612: 5611: 5610: 5605: 5598: 5597: 5596: 5591: 5586: 5581: 5576: 5566: 5561: 5560: 5559: 5558: 5553: 5548: 5543: 5536: 5535: 5534: 5527: 5526: 5525: 5520: 5515: 5508: 5507: 5506: 5501: 5496: 5491: 5484: 5483: 5482: 5477: 5470: 5469: 5468: 5463: 5458: 5453: 5448: 5443: 5438: 5433: 5423: 5418: 5416: 5410: 5409: 5407: 5406: 5405: 5404: 5399: 5394: 5389: 5384: 5379: 5374: 5369: 5364: 5359: 5354: 5349: 5344: 5339: 5334: 5323: 5321: 5315: 5314: 5312: 5311: 5310: 5309: 5304: 5299: 5294: 5289: 5284: 5275: 5271: 5270: 5269: 5264: 5259: 5254: 5245: 5237: 5236: 5235: 5230: 5225: 5220: 5215: 5210: 5201: 5197: 5193: 5188: 5186: 5180: 5179: 5177: 5176: 5175: 5174: 5169: 5164: 5159: 5154: 5149: 5144: 5139: 5130: 5126: 5125: 5124: 5116: 5115: 5114: 5109: 5104: 5094: 5093: 5092: 5087: 5082: 5077: 5072: 5061: 5059: 5049: 5048: 5033: 5032: 5029: 5028: 5025: 5024: 5022: 5021: 5020: 5019: 5014: 5009: 5004: 4994: 4990: 4989: 4988: 4983: 4978: 4973: 4968: 4963: 4958: 4953: 4948: 4943: 4933: 4928: 4926: 4920: 4919: 4917: 4916: 4915: 4914: 4909: 4904: 4899: 4888: 4886: 4879: 4878: 4876: 4875: 4874: 4873: 4868: 4863: 4858: 4847: 4845: 4837: 4836: 4833:Sodium channel 4821: 4820: 4817: 4816: 4813: 4812: 4810: 4809: 4808: 4807: 4802: 4792: 4791: 4790: 4785: 4780: 4775: 4764: 4763: 4762: 4761: 4756: 4751: 4746: 4736: 4735: 4734: 4729: 4724: 4719: 4709: 4708: 4707: 4702: 4692: 4687: 4686: 4685: 4684: 4679: 4674: 4664: 4656: 4651: 4643: 4638: 4630: 4629: 4628: 4618: 4610: 4605: 4597: 4596: 4595: 4590: 4585: 4580: 4570: 4561: 4559: 4553: 4552: 4550: 4549: 4548: 4547: 4542: 4537: 4527: 4526: 4525: 4520: 4515: 4504: 4502: 4494: 4493: 4478: 4477: 4461: 4460: 4453: 4446: 4438: 4432: 4431: 4408: 4396: 4395:External links 4393: 4391: 4390: 4361:(1): 367–377. 4341: 4284: 4249: 4200: 4169:(7): 4782–91. 4149: 4098: 4049: 4020:(6): 693–715. 3997: 3968:(6): 1065–83. 3948: 3933: 3907: 3872:(1): 192–199. 3852: 3815:(2): 245–251. 3795: 3758:(4): 721–726. 3737: 3700:(6): 965–976. 3680: 3612: 3575:(7): 624–629. 3552: 3493: 3456:(3): 488–499. 3433: 3396:(8): 873–880. 3372: 3304: 3267:(2): 371–383. 3242: 3184: 3163:(2): 287–300. 3143: 3097: 3060:(6): 899–911. 3033: 2979: 2930: 2889: 2830: 2781: 2737: 2688: 2639: 2612:(6): 397–407. 2596: 2555: 2514: 2487: 2443: 2394: 2343: 2294: 2245: 2195: 2152: 2101: 2053: 2024: 1974: 1947:(4): 397–409. 1924: 1876: 1864: 1852: 1840: 1828: 1819: 1782:Genome Biology 1768: 1753: 1727: 1720: 1699: 1678: 1647: 1645: 1642: 1640: 1639: 1633: 1624: 1618: 1612: 1606: 1599: 1597: 1594: 1589: 1585: 1581: 1577: 1573: 1569: 1565: 1561: 1557: 1553: 1549: 1545: 1542: 1536: 1533: 1523: 1520: 1514: 1511: 1505: 1502: 1492: 1489: 1483: 1480: 1469: 1450:both activate 1415: 1412: 1406: 1403: 1402: 1401: 1400: 1399: 1396:Scorpion venom 1393: 1388: 1382:-based toxins 1372: 1369: 1368: 1367: 1366: 1365: 1360: 1353: 1348: 1343: 1338: 1333: 1327:-based toxins 1311: 1308: 1303:Main article: 1300: 1297: 1295: 1292: 1237:Main article: 1234: 1231: 1204: 1201: 1198: 1197: 1194: 1191: 1187: 1183: 1179: 1176: 1169: 1164: 1159: 1158: 1153: 1150: 1146: 1142: 1138: 1135: 1128: 1123: 1118: 1117: 1112: 1109: 1105: 1101: 1097: 1093: 1090: 1083: 1078: 1073: 1072: 1066: 1063: 1059: 1055: 1052: 1045: 1040: 1035: 1034: 1028: 1025: 1024:Assembles with 1022: 1017: 960: 957: 951: 948: 945: 944: 941: 938: 931: 927: 922: 921: 918: 915: 908: 903: 898: 897: 894: 891: 884: 879: 874: 873: 855: 842: 835: 830: 825: 824: 807: 796: 789: 784: 779: 778: 748: 745: 738: 733: 728: 727: 714: 709: 702: 697: 692: 691: 688: 685: 678: 673: 668: 667: 653: 650: 643: 638: 633: 632: 605: 596: 589: 584: 579: 578: 572: 569: 566: 546: 542: 541:1.1 through Na 538: 515: 514:Alpha subunits 512: 506: 503: 474: 471: 454:Hodgkin–Huxley 445: 442: 430:deinactivation 415: 414: 411: 408: 405: 402: 398: 397: 394: 391: 388: 385: 381: 380: 377: 374: 371: 368: 364: 363: 360: 357: 354: 351: 347: 346: 343: 340: 337: 334: 330: 329: 326: 323: 320: 317: 313: 312: 309: 306: 303: 300: 296: 295: 292: 289: 286: 283: 253: 250: 227:alpha subunits 206: 203: 198:Main article: 195: 192: 186: 183: 154: 151: 148: 147: 144: 141: 137: 136: 129: 126: 120: 119: 112: 110: 109: 106: 103: 100: 96: 94: 88: 87: 82: 79: 69: 68:Classification 66: 26: 9: 6: 4: 3: 2: 9793: 9782: 9779: 9777: 9774: 9772: 9769: 9768: 9766: 9753: 9752: 9748: 9745: 9739: 9728: 9724: 9723: 9721: 9716: 9710: 9703: 9699: 9698: 9696: 9691: 9685: 9682: 9678: 9664: 9661: 9659: 9656: 9654: 9651: 9649: 9648:Niflumic acid 9646: 9644: 9641: 9639: 9636: 9634: 9631: 9629: 9626: 9624: 9621: 9620: 9618: 9616: 9612: 9609: 9605: 9595: 9592: 9590: 9587: 9585: 9582: 9580: 9577: 9575: 9572: 9570: 9567: 9566: 9564: 9562: 9558: 9552: 9549: 9547: 9544: 9542: 9541:Glibenclamide 9539: 9538: 9536: 9534: 9530: 9527: 9522: 9516: 9506: 9503: 9502: 9500: 9498: 9494: 9488: 9487:Niflumic acid 9485: 9483: 9480: 9478: 9475: 9473: 9472:Glibenclamide 9470: 9468: 9465: 9463: 9460: 9458: 9455: 9453: 9450: 9448: 9445: 9443: 9440: 9439: 9437: 9435: 9431: 9428: 9423: 9417: 9414: 9412: 9408: 9394: 9391: 9389: 9386: 9384: 9381: 9379: 9376: 9374: 9371: 9370: 9368: 9366: 9362: 9359: 9354: 9348: 9338: 9335: 9334: 9332: 9330: 9326: 9320: 9317: 9315: 9312: 9310: 9307: 9306: 9304: 9302: 9298: 9295: 9290: 9284: 9274: 9271: 9269: 9268:Grayanotoxins 9266: 9264: 9261: 9259: 9258:Batrachotoxin 9256: 9253: 9249: 9245: 9244:ω-Atracotoxin 9241: 9239: 9236: 9235: 9233: 9231: 9227: 9221: 9218: 9216: 9213: 9210: 9206: 9203: 9201: 9198: 9196: 9195:Buprenorphine 9193: 9190: 9189: 9186: 9183: 9181: 9178: 9176: 9173: 9171: 9168: 9166: 9163: 9160: 9159: 9156: 9153: 9151: 9148: 9146: 9143: 9141: 9138: 9136: 9133: 9131: 9128: 9126: 9123: 9121: 9118: 9116: 9113: 9111: 9108: 9105: 9104: 9101: 9098: 9096: 9093: 9091: 9088: 9086: 9083: 9081: 9078: 9076: 9073: 9071: 9068: 9066: 9063: 9061: 9058: 9056: 9053: 9051: 9048: 9046: 9043: 9041: 9038: 9036: 9033: 9031: 9028: 9026: 9023: 9021: 9018: 9016: 9013: 9011: 9008: 9006: 9003: 9001: 8998: 8996: 8993: 8991: 8988: 8986: 8983: 8980: 8976: 8972: 8969: 8967: 8964: 8962: 8959: 8957: 8954: 8952: 8950: 8946: 8943: 8942: 8939: 8936: 8934: 8931: 8929: 8928:Valproic acid 8926: 8924: 8921: 8919: 8916: 8914: 8911: 8909: 8906: 8904: 8901: 8899: 8896: 8894: 8891: 8889: 8886: 8884: 8881: 8879: 8876: 8874: 8873:Oxitriptyline 8871: 8869: 8868:Oxcarbazepine 8866: 8864: 8861: 8859: 8858:Licarbazepine 8856: 8854: 8851: 8849: 8846: 8844: 8841: 8839: 8836: 8834: 8831: 8829: 8826: 8824: 8821: 8819: 8816: 8814: 8813:Carbamazepine 8811: 8809: 8806: 8803: 8802: 8799: 8796: 8794: 8791: 8789: 8786: 8784: 8781: 8779: 8776: 8774: 8771: 8769: 8766: 8764: 8761: 8759: 8756: 8754: 8751: 8749: 8746: 8744: 8741: 8739: 8736: 8734: 8731: 8729: 8726: 8724: 8721: 8719: 8716: 8714: 8711: 8708: 8707: 8704: 8701: 8700:Antianginals: 8698: 8697: 8695: 8693: 8689: 8686: 8681: 8675: 8672: 8670: 8666: 8652: 8649: 8648: 8646: 8644: 8640: 8634: 8633:Norfluoxetine 8631: 8629: 8626: 8624: 8621: 8619: 8616: 8615: 8613: 8611: 8607: 8604: 8599: 8593: 8583: 8580: 8578: 8575: 8573: 8570: 8568: 8567:Niflumic acid 8565: 8563: 8560: 8558: 8555: 8553: 8546: 8545: 8543: 8541: 8537: 8531: 8528: 8526: 8523: 8521: 8514: 8513: 8511: 8509: 8505: 8502: 8497: 8488: 8478: 8475: 8470: 8464: 8463: 8460: 8457: 8455: 8452: 8450: 8447: 8445: 8442: 8440: 8437: 8435: 8432: 8430: 8427: 8425: 8422: 8420: 8419:Levcromakalim 8417: 8415: 8412: 8410: 8407: 8405: 8402: 8400: 8397: 8395: 8392: 8387: 8378: 8377: 8375: 8373: 8369: 8363: 8360: 8358: 8355: 8353: 8350: 8348: 8345: 8343: 8340: 8338: 8335: 8333: 8330: 8328: 8325: 8323: 8320: 8315: 8309: 8308: 8305: 8302: 8300: 8297: 8295: 8292: 8290: 8287: 8285: 8282: 8280: 8277: 8275: 8272: 8270: 8267: 8265: 8262: 8260: 8257: 8255: 8252: 8250: 8247: 8245: 8242: 8240: 8237: 8235: 8232: 8230: 8227: 8225: 8222: 8220: 8217: 8215: 8214:Acetohexamide 8212: 8207: 8198: 8197: 8195: 8193: 8189: 8186: 8181: 8175: 8165: 8162: 8160: 8157: 8155: 8147: 8146: 8144: 8142: 8138: 8132: 8129: 8127: 8124: 8122: 8119: 8117: 8109: 8108: 8105: 8102: 8100: 8097: 8095: 8092: 8090: 8087: 8085: 8082: 8080: 8077: 8075: 8072: 8070: 8067: 8065: 8062: 8060: 8059:Roxithromycin 8057: 8055: 8052: 8050: 8047: 8045: 8042: 8040: 8037: 8035: 8032: 8030: 8027: 8025: 8022: 8020: 8017: 8015: 8012: 8010: 8007: 8005: 8002: 8000: 7997: 7995: 7992: 7990: 7987: 7985: 7982: 7980: 7977: 7975: 7972: 7970: 7967: 7965: 7962: 7960: 7957: 7955: 7952: 7950: 7947: 7945: 7942: 7940: 7937: 7935: 7932: 7930: 7927: 7925: 7922: 7920: 7917: 7915: 7912: 7910: 7907: 7905: 7902: 7896: 7892: 7891: 7888: 7885: 7883: 7880: 7878: 7875: 7873: 7870: 7868: 7865: 7863: 7860: 7858: 7855: 7853: 7850: 7848: 7845: 7843: 7840: 7838: 7835: 7833: 7830: 7828: 7825: 7823: 7820: 7818: 7815: 7813: 7810: 7808: 7805: 7803: 7800: 7798: 7795: 7793: 7790: 7788: 7785: 7783: 7780: 7778: 7775: 7773: 7770: 7768: 7765: 7763: 7760: 7758: 7755: 7753: 7752:Charybdotoxin 7750: 7748: 7745: 7743: 7740: 7738: 7735: 7733: 7730: 7728: 7725: 7723: 7720: 7718: 7715: 7713: 7710: 7709: 7707: 7705: 7701: 7698: 7693: 7687: 7684: 7682: 7678: 7664: 7661: 7659: 7655: 7654: 7652: 7650: 7646: 7640: 7637: 7635: 7634:Trimethadione 7632: 7630: 7627: 7625: 7622: 7620: 7617: 7615: 7612: 7610: 7607: 7605: 7602: 7600: 7597: 7595: 7592: 7590: 7587: 7585: 7582: 7580: 7577: 7575: 7572: 7570: 7567: 7565: 7562: 7560: 7557: 7555: 7552: 7550: 7547: 7545: 7542: 7540: 7537: 7535: 7532: 7530: 7527: 7525: 7522: 7520: 7517: 7515: 7512: 7510: 7507: 7505: 7502: 7500: 7497: 7495: 7492: 7490: 7487: 7485: 7482: 7480: 7477: 7475: 7474:Diproteverine 7472: 7470: 7467: 7465: 7462: 7460: 7457: 7455: 7452: 7450: 7447: 7445: 7442: 7440: 7437: 7435: 7432: 7429: 7428: 7425: 7422: 7420: 7417: 7415: 7412: 7410: 7407: 7405: 7402: 7400: 7397: 7395: 7392: 7390: 7387: 7385: 7382: 7380: 7377: 7375: 7372: 7370: 7367: 7365: 7362: 7360: 7357: 7355: 7351: 7343: 7342: 7339: 7336: 7334: 7333:Ruthenium red 7331: 7329: 7326: 7324: 7321: 7319: 7316: 7314: 7311: 7309: 7308:Levetiracetam 7306: 7304: 7301: 7299: 7296: 7294: 7291: 7289: 7286: 7284: 7281: 7279: 7276: 7274: 7271: 7269: 7266: 7264: 7261: 7259: 7258:ω-Agatoxin TK 7256: 7253: 7252: 7249: 7246: 7244: 7241: 7239: 7236: 7234: 7231: 7229: 7228:Niflumic acid 7226: 7224: 7221: 7219: 7216: 7214: 7210: 7209: 7206: 7203: 7201: 7197: 7196: 7193: 7190: 7188: 7185: 7183: 7179: 7178: 7175: 7172: 7170: 7167: 7165: 7162: 7160: 7157: 7155: 7152: 7150: 7147: 7145: 7142: 7140: 7137: 7135: 7132: 7130: 7127: 7125: 7121: 7120: 7117: 7114: 7112: 7109: 7107: 7104: 7102: 7099: 7097: 7094: 7092: 7089: 7087: 7084: 7082: 7079: 7077: 7074: 7070: 7067: 7065: 7062: 7060: 7057: 7055: 7052: 7050: 7047: 7045: 7042: 7040: 7037: 7035: 7032: 7030: 7027: 7025: 7022: 7020: 7017: 7015: 7012: 7010: 7007: 7005: 7002: 7000: 6995: 6992: 6990: 6987: 6985: 6982: 6980: 6977: 6975: 6972: 6970: 6965: 6962: 6960: 6957: 6955: 6952: 6950: 6947: 6945: 6942: 6940: 6937: 6935: 6932: 6930: 6927: 6925: 6922: 6920: 6917: 6915: 6912: 6910: 6907: 6905: 6902: 6900: 6897: 6895: 6892: 6890: 6887: 6885: 6882: 6880: 6877: 6875: 6872: 6870: 6867: 6865: 6862: 6860: 6857: 6855: 6852: 6850: 6849:Levamlodipine 6847: 6845: 6844:Lercanidipine 6842: 6840: 6837: 6835: 6832: 6830: 6827: 6825: 6822: 6820: 6817: 6815: 6812: 6810: 6807: 6805: 6802: 6800: 6797: 6795: 6792: 6790: 6787: 6785: 6782: 6780: 6777: 6775: 6772: 6770: 6767: 6765: 6762: 6760: 6757: 6755: 6751: 6749: 6745: 6744: 6742: 6740: 6736: 6733: 6728: 6722: 6719: 6717: 6713: 6709: 6702: 6697: 6695: 6690: 6688: 6683: 6682: 6679: 6669: 6668: 6661: 6647: 6644: 6642: 6641:Voltage-gated 6639: 6637: 6634: 6632: 6629: 6628: 6626: 6624: 6620: 6616: 6612: 6607: 6603: 6589: 6586: 6580: 6577: 6575: 6572: 6570: 6567: 6566: 6564: 6560: 6557: 6555: 6552: 6550: 6547: 6546: 6544: 6540: 6537: 6535: 6532: 6530: 6527: 6525: 6522: 6520: 6517: 6515: 6512: 6510: 6507: 6506: 6504: 6500: 6497: 6495: 6492: 6490: 6487: 6485: 6482: 6480: 6477: 6475: 6472: 6470: 6467: 6466: 6464: 6463: 6462: 6459: 6458: 6456: 6454: 6451: 6449: 6444: 6438: 6435: 6431: 6428: 6426: 6423: 6421: 6418: 6417: 6416: 6413: 6409: 6406: 6404: 6401: 6399: 6396: 6394: 6391: 6389: 6386: 6384: 6381: 6379: 6376: 6374: 6371: 6369: 6366: 6364: 6361: 6360: 6359: 6356: 6355: 6353: 6351: 6348: 6346: 6342: 6333: 6325: 6322: 6320: 6317: 6315: 6312: 6310: 6307: 6305: 6302: 6300: 6297: 6296: 6295: 6292: 6288: 6285: 6283: 6280: 6279: 6278: 6275: 6273: 6270: 6266: 6263: 6261: 6258: 6256: 6253: 6252: 6251: 6248: 6244: 6241: 6239: 6236: 6234: 6231: 6229: 6226: 6224: 6221: 6219: 6216: 6214: 6211: 6209: 6206: 6205: 6204: 6201: 6197: 6194: 6192: 6189: 6187: 6184: 6182: 6179: 6177: 6174: 6172: 6169: 6167: 6164: 6162: 6159: 6158: 6157: 6154: 6151: 6147: 6144: 6143: 6141: 6139: 6136: 6134: 6129: 6121: 6118: 6116: 6113: 6111: 6108: 6106: 6103: 6101: 6098: 6097: 6096: 6095: 6091: 6087: 6084: 6082: 6079: 6077: 6074: 6073: 6072: 6069: 6065: 6062: 6060: 6057: 6055: 6052: 6050: 6047: 6046: 6045: 6042: 6041: 6039: 6037: 6034: 6032: 6027: 6021: 6018: 6017: 6015: 6013: 6010: 6008: 6003: 5995: 5992: 5990: 5987: 5986: 5985: 5982: 5978: 5975: 5973: 5970: 5968: 5965: 5963: 5960: 5958: 5955: 5953: 5950: 5948: 5945: 5944: 5943: 5940: 5936: 5933: 5931: 5928: 5926: 5923: 5921: 5918: 5916: 5913: 5911: 5908: 5906: 5903: 5901: 5898: 5896: 5893: 5892: 5891: 5888: 5886: 5883: 5877: 5874: 5872: 5869: 5867: 5864: 5862: 5859: 5858: 5857: 5854: 5850: 5847: 5845: 5842: 5841: 5840: 5837: 5833: 5830: 5829: 5828: 5825: 5824: 5823: 5820: 5819: 5817: 5815: 5812: 5810: 5805: 5801: 5797: 5796:Miscellaneous 5792: 5788: 5774: 5773:Shaker (gene) 5771: 5767: 5764: 5762: 5759: 5757: 5754: 5753: 5752: 5749: 5747: 5746:minK/ISK-like 5744: 5742: 5739: 5735: 5732: 5730: 5727: 5725: 5722: 5720: 5717: 5716: 5715: 5712: 5708: 5705: 5703: 5700: 5698: 5695: 5694: 5693: 5686: 5685: 5680: 5677: 5675: 5672: 5670: 5667: 5666: 5665: 5661: 5658: 5656: 5653: 5651: 5648: 5647: 5646: 5642: 5639: 5637: 5634: 5633: 5632: 5628: 5625: 5623: 5620: 5618: 5615: 5614: 5613: 5609: 5606: 5604: 5601: 5600: 5599: 5595: 5592: 5590: 5587: 5585: 5582: 5580: 5577: 5575: 5572: 5571: 5570: 5563: 5562: 5557: 5554: 5552: 5549: 5547: 5544: 5542: 5539: 5538: 5537: 5533: 5530: 5529: 5528: 5524: 5521: 5519: 5516: 5514: 5511: 5510: 5509: 5505: 5502: 5500: 5497: 5495: 5492: 5490: 5487: 5486: 5485: 5481: 5478: 5476: 5473: 5472: 5471: 5467: 5464: 5462: 5459: 5457: 5454: 5452: 5449: 5447: 5444: 5442: 5439: 5437: 5434: 5432: 5429: 5428: 5427: 5420: 5419: 5417: 5415: 5414:Voltage-gated 5411: 5403: 5400: 5398: 5395: 5393: 5390: 5388: 5385: 5383: 5380: 5378: 5375: 5373: 5370: 5368: 5365: 5363: 5360: 5358: 5355: 5353: 5350: 5348: 5345: 5343: 5340: 5338: 5335: 5333: 5330: 5329: 5328: 5325: 5324: 5322: 5320: 5316: 5308: 5305: 5303: 5300: 5298: 5295: 5293: 5290: 5288: 5285: 5283: 5280: 5279: 5278: 5272: 5268: 5265: 5263: 5260: 5258: 5255: 5253: 5250: 5249: 5248: 5241: 5238: 5234: 5231: 5229: 5226: 5224: 5221: 5219: 5216: 5214: 5211: 5209: 5206: 5205: 5204: 5198: 5196: 5190: 5189: 5187: 5185: 5181: 5173: 5170: 5168: 5165: 5163: 5160: 5158: 5155: 5153: 5150: 5148: 5145: 5143: 5140: 5138: 5135: 5134: 5133: 5127: 5123: 5120: 5119: 5117: 5113: 5110: 5108: 5105: 5103: 5100: 5099: 5098: 5095: 5091: 5088: 5086: 5083: 5081: 5078: 5076: 5073: 5071: 5068: 5067: 5066: 5063: 5062: 5060: 5058: 5054: 5050: 5046: 5043: 5038: 5034: 5018: 5015: 5013: 5010: 5008: 5005: 5003: 5000: 4999: 4998: 4991: 4987: 4984: 4982: 4979: 4977: 4974: 4972: 4969: 4967: 4964: 4962: 4959: 4957: 4954: 4952: 4949: 4947: 4944: 4942: 4939: 4938: 4937: 4930: 4929: 4927: 4925: 4924:Voltage-gated 4921: 4913: 4910: 4908: 4905: 4903: 4900: 4898: 4895: 4894: 4893: 4890: 4889: 4887: 4884: 4880: 4872: 4869: 4867: 4864: 4862: 4859: 4857: 4854: 4853: 4852: 4849: 4848: 4846: 4842: 4838: 4834: 4831: 4826: 4822: 4806: 4803: 4801: 4798: 4797: 4796: 4793: 4789: 4786: 4784: 4781: 4779: 4776: 4774: 4771: 4770: 4769: 4766: 4765: 4760: 4757: 4755: 4752: 4750: 4747: 4745: 4742: 4741: 4740: 4737: 4733: 4730: 4728: 4725: 4723: 4720: 4718: 4715: 4714: 4713: 4710: 4706: 4703: 4701: 4698: 4697: 4696: 4689: 4688: 4683: 4680: 4678: 4675: 4673: 4670: 4669: 4668: 4660: 4657: 4655: 4647: 4644: 4642: 4634: 4631: 4627: 4624: 4623: 4622: 4614: 4611: 4609: 4601: 4598: 4594: 4591: 4589: 4586: 4584: 4581: 4579: 4576: 4575: 4574: 4566: 4563: 4562: 4560: 4558: 4557:Voltage-gated 4554: 4546: 4543: 4541: 4538: 4536: 4533: 4532: 4531: 4528: 4524: 4521: 4519: 4516: 4514: 4511: 4510: 4509: 4506: 4505: 4503: 4499: 4495: 4491: 4488: 4483: 4479: 4474: 4470: 4466: 4459: 4454: 4452: 4447: 4445: 4440: 4439: 4436: 4422:on 2021-12-09 4421: 4417: 4413: 4409: 4406: 4402: 4399: 4398: 4386: 4382: 4377: 4372: 4368: 4364: 4360: 4356: 4352: 4345: 4337: 4333: 4328: 4323: 4319: 4315: 4311: 4307: 4303: 4299: 4295: 4288: 4280: 4276: 4272: 4268: 4264: 4260: 4253: 4245: 4241: 4236: 4231: 4227: 4223: 4219: 4215: 4211: 4204: 4196: 4192: 4187: 4182: 4177: 4172: 4168: 4164: 4160: 4153: 4145: 4141: 4136: 4131: 4126: 4121: 4117: 4113: 4109: 4102: 4094: 4090: 4085: 4080: 4076: 4072: 4068: 4064: 4060: 4053: 4045: 4041: 4036: 4031: 4027: 4023: 4019: 4015: 4011: 4004: 4002: 3993: 3989: 3984: 3979: 3975: 3971: 3967: 3963: 3959: 3952: 3944: 3940: 3936: 3930: 3926: 3922: 3918: 3911: 3903: 3899: 3895: 3891: 3887: 3883: 3879: 3875: 3871: 3867: 3863: 3856: 3848: 3844: 3839: 3834: 3830: 3826: 3822: 3818: 3814: 3810: 3806: 3799: 3791: 3787: 3782: 3777: 3773: 3769: 3765: 3761: 3757: 3753: 3749: 3741: 3733: 3729: 3725: 3721: 3717: 3713: 3708: 3703: 3699: 3695: 3691: 3684: 3676: 3672: 3667: 3662: 3658: 3654: 3650: 3646: 3642: 3638: 3634: 3630: 3626: 3619: 3617: 3608: 3604: 3600: 3596: 3592: 3588: 3583: 3578: 3574: 3570: 3566: 3559: 3557: 3548: 3544: 3539: 3534: 3530: 3526: 3521: 3516: 3512: 3508: 3504: 3497: 3489: 3485: 3480: 3475: 3471: 3467: 3463: 3459: 3455: 3451: 3447: 3440: 3438: 3429: 3425: 3420: 3415: 3411: 3407: 3403: 3399: 3395: 3391: 3387: 3379: 3377: 3368: 3364: 3359: 3354: 3350: 3346: 3342: 3338: 3334: 3330: 3326: 3322: 3318: 3311: 3309: 3300: 3296: 3292: 3288: 3284: 3280: 3275: 3270: 3266: 3262: 3258: 3251: 3249: 3247: 3238: 3234: 3230: 3226: 3222: 3218: 3214: 3210: 3206: 3202: 3198: 3191: 3189: 3180: 3176: 3171: 3166: 3162: 3158: 3154: 3147: 3139: 3135: 3130: 3125: 3121: 3117: 3113: 3109: 3101: 3093: 3089: 3084: 3079: 3075: 3071: 3067: 3063: 3059: 3055: 3051: 3044: 3042: 3040: 3038: 3029: 3025: 3020: 3015: 3011: 3007: 3003: 2999: 2995: 2988: 2986: 2984: 2975: 2971: 2966: 2961: 2957: 2953: 2950:(2): 427–34. 2949: 2945: 2941: 2934: 2926: 2922: 2917: 2912: 2908: 2904: 2900: 2893: 2885: 2881: 2876: 2871: 2866: 2861: 2857: 2853: 2849: 2845: 2841: 2834: 2826: 2822: 2817: 2812: 2808: 2804: 2800: 2796: 2792: 2785: 2777: 2773: 2769: 2765: 2761: 2757: 2753: 2749: 2741: 2733: 2729: 2724: 2719: 2715: 2711: 2707: 2703: 2699: 2692: 2684: 2680: 2675: 2670: 2666: 2662: 2658: 2654: 2650: 2643: 2635: 2631: 2627: 2623: 2619: 2615: 2611: 2607: 2600: 2592: 2588: 2583: 2578: 2574: 2570: 2566: 2559: 2551: 2547: 2542: 2537: 2533: 2529: 2525: 2518: 2504: 2497: 2491: 2483: 2479: 2475: 2471: 2467: 2463: 2459: 2455: 2447: 2439: 2435: 2431: 2427: 2422: 2417: 2413: 2409: 2405: 2398: 2390: 2386: 2381: 2376: 2371: 2366: 2362: 2358: 2354: 2347: 2339: 2335: 2330: 2325: 2321: 2317: 2314:(8): 2010–7. 2313: 2309: 2305: 2298: 2290: 2286: 2281: 2276: 2272: 2268: 2264: 2260: 2256: 2249: 2241: 2237: 2232: 2227: 2223: 2219: 2215: 2211: 2207: 2199: 2191: 2187: 2183: 2179: 2175: 2171: 2167: 2163: 2156: 2148: 2144: 2139: 2134: 2129: 2124: 2120: 2116: 2112: 2105: 2097: 2093: 2088: 2083: 2079: 2075: 2071: 2064: 2062: 2060: 2058: 2050: 2039: 2035: 2028: 2020: 2016: 2011: 2006: 2002: 1998: 1994: 1990: 1986: 1978: 1970: 1966: 1962: 1958: 1954: 1950: 1946: 1942: 1938: 1931: 1929: 1920: 1916: 1912: 1908: 1904: 1900: 1896: 1892: 1885: 1883: 1881: 1874: 1868: 1862: 1856: 1850: 1844: 1838: 1832: 1823: 1815: 1811: 1806: 1801: 1796: 1791: 1787: 1783: 1779: 1772: 1764: 1760: 1756: 1750: 1746: 1742: 1738: 1731: 1723: 1717: 1713: 1709: 1708:Bertil Hillel 1703: 1695: 1689: 1681: 1675: 1671: 1666: 1665: 1659: 1652: 1648: 1637: 1634: 1628: 1625: 1622: 1619: 1616: 1613: 1610: 1607: 1604: 1601: 1600: 1593: 1541: 1532: 1530: 1519: 1513:pH modulation 1510: 1501: 1498: 1488: 1479: 1477: 1473: 1465: 1464:Acetylcholine 1461: 1457: 1453: 1449: 1445: 1441: 1437: 1428: 1424: 1422: 1411: 1397: 1394: 1392: 1391:δ-Atracotoxin 1389: 1387: 1384: 1383: 1381: 1378: 1377: 1376: 1364: 1361: 1358: 1357:grayanotoxins 1354: 1352: 1349: 1347: 1344: 1342: 1339: 1337: 1336:batrachotoxin 1334: 1332: 1329: 1328: 1326: 1323: 1322: 1321: 1317: 1306: 1291: 1287: 1285: 1281: 1276: 1274: 1270: 1266: 1262: 1258: 1254: 1250: 1246: 1240: 1230: 1228: 1227:acetylcholine 1224: 1220: 1215: 1213: 1209: 1195: 1192: 1177: 1175: 1174: 1170: 1168: 1161: 1160: 1157: 1154: 1151: 1136: 1134: 1133: 1129: 1127: 1120: 1119: 1116: 1113: 1110: 1091: 1089: 1088: 1084: 1082: 1075: 1074: 1071: 1067: 1064: 1053: 1051: 1050: 1046: 1044: 1037: 1036: 1033: 1029: 1026: 1023: 1021: 1018: 1016: 1013: 1012: 1008: 1003: 1001: 997: 993: 989: 985: 981: 977: 973: 969: 966: 965:intracellular 956: 950:Beta subunits 942: 939: 937: 936: 932: 930: 924: 923: 919: 916: 914: 913: 909: 907: 900: 899: 895: 892: 890: 889: 885: 883: 876: 875: 871: 867: 863: 859: 856: 854: 850: 849:Schwann cells 846: 843: 841: 840: 836: 834: 827: 826: 823: 819: 815: 811: 808: 805: 801: 797: 795: 794: 790: 788: 781: 780: 777: 775: 769: 765: 761: 757: 753: 749: 746: 744: 743: 739: 737: 730: 729: 726: 722: 718: 715: 713: 710: 708: 707: 703: 701: 694: 693: 689: 686: 684: 683: 679: 677: 670: 669: 666: 662: 658: 654: 651: 649: 648: 644: 642: 635: 634: 630: 626: 622: 618: 614: 610: 606: 604: 600: 597: 595: 594: 590: 588: 581: 580: 577: 573: 570: 567: 564: 563: 559: 554: 550: 535: 533: 524: 520: 511: 502: 500: 499:glutamic acid 496: 492: 488: 484: 480: 470: 467: 463: 459: 455: 451: 441: 439: 433: 431: 426: 424: 423: 412: 409: 406: 403: 400: 399: 395: 392: 389: 386: 383: 382: 378: 375: 372: 369: 366: 365: 361: 358: 355: 352: 349: 348: 344: 341: 338: 335: 332: 331: 327: 324: 321: 318: 315: 314: 310: 307: 304: 301: 298: 297: 293: 290: 287: 284: 281: 280: 277: 275: 271: 267: 263: 258: 249: 245: 243: 239: 234: 232: 231:beta subunits 228: 220: 216: 215:glycosylation 211: 201: 191: 182: 180: 176: 172: 168: 164: 160: 145: 142: 139: 138: 134: 130: 127: 125: 122: 121: 117: 113: 108:"Nav channel" 107: 104: 101: 98: 97: 95: 93: 90: 89: 83: 80: 77: 76: 73: 65: 63: 59: 56: 52: 49:, conducting 48: 44: 40: 32: 19: 9743: 9742: 9653:Talniflumate 9191: 9180:Tetrodotoxin 9170:Neosaxitoxin 9161: 9106: 9080:Propoxycaine 9015:Dimethocaine 8948: 8944: 8913:Valnoctamide 8843:Fosphenytoin 8804: 8778:Procainamide 8768:Pilsicainide 8723:Disopyramide 8709: 8699: 8668: 8547: 8515: 8465: 8379: 8347:Ethosuximide 8332:Cloperastine 8310: 8279:Metahexamide 8274:Glycyclamide 8234:Glibornuride 8199: 8148: 8110: 8089:Thioridazine 8044:Promethazine 8029:Orphenadrine 8019:Ketoconazole 8004:Erythromycin 7893: 7656: 7584:Phensuximide 7564:Ochratoxin A 7504:Ethosuximide 7430: 7352:-selective ( 7344: 7254: 7211: 7198: 7180: 7129:ω-Conotoxins 7122: 7072: 7054:Norverapamil 7019:Dexverapamil 6997: 6971:derivatives: 6967: 6964:Vatanidipine 6959:Trombodipine 6924:Palonidipine 6909:Nitrendipine 6864:Mepirodipine 6769:Azelnidipine 6752: 6746: 6664: 6631:Ligand-gated 6622: 6610: 6453:Gap junction 6446: 6335: 6131: 6092: 6070: 6043: 6029: 6005: 5983: 5941: 5889: 5855: 5838: 5826: 5807: 5795: 5750: 5713: 5687: 5564: 5421: 5326: 5273: 5243: 5199: 5128: 5041: 4992: 4931: 4832: 4829: 4738: 4711: 4690: 4662: 4649: 4636: 4616: 4603: 4568: 4501:Ligand-gated 4486: 4469:ion channels 4424:. Retrieved 4420:the original 4415: 4358: 4354: 4344: 4301: 4297: 4287: 4265:(3): 304–8. 4262: 4258: 4252: 4217: 4213: 4203: 4166: 4162: 4152: 4115: 4111: 4101: 4066: 4062: 4052: 4017: 4013: 3965: 3961: 3951: 3916: 3910: 3869: 3865: 3855: 3812: 3808: 3798: 3755: 3751: 3740: 3697: 3693: 3683: 3632: 3628: 3572: 3568: 3510: 3507:PLOS Biology 3506: 3496: 3453: 3449: 3393: 3390:EMBO Reports 3389: 3324: 3320: 3264: 3260: 3204: 3201:FEBS Letters 3200: 3160: 3156: 3146: 3111: 3107: 3100: 3057: 3053: 3001: 2997: 2947: 2943: 2933: 2906: 2902: 2892: 2847: 2843: 2833: 2798: 2794: 2784: 2751: 2747: 2740: 2705: 2701: 2691: 2656: 2652: 2642: 2609: 2605: 2599: 2572: 2568: 2558: 2531: 2527: 2517: 2506:. Retrieved 2502: 2490: 2457: 2453: 2446: 2414:(1): 13–25. 2411: 2407: 2397: 2360: 2356: 2346: 2311: 2307: 2297: 2262: 2258: 2248: 2213: 2209: 2198: 2165: 2161: 2155: 2118: 2114: 2104: 2077: 2073: 2048: 2042:. Retrieved 2027: 1992: 1988: 1977: 1944: 1940: 1897:(1): 42–54. 1894: 1890: 1867: 1855: 1843: 1831: 1822: 1785: 1781: 1771: 1736: 1730: 1711: 1702: 1663: 1656:Jessell TM, 1651: 1547: 1538: 1525: 1516: 1507: 1494: 1485: 1436:tetrodotoxin 1433: 1417: 1408: 1374: 1319: 1288: 1277: 1260: 1257:depolarizing 1242: 1216: 1208:Ligand-gated 1206: 1171: 1130: 1085: 1047: 1019: 1015:Protein name 1014: 1006: 968:cytoskeleton 962: 953: 933: 910: 886: 870:fibromyalgia 837: 791: 771: 740: 704: 680: 645: 628: 624: 620: 591: 565:Protein name 557: 551: 536: 528: 522: 508: 476: 447: 437: 434: 429: 427: 420: 418: 379:Repolarized 345:Depolarized 273: 269: 265: 259: 255: 246: 235: 224: 188: 175:rising phase 156: 71: 47:ion channels 38: 37: 9319:Triamterene 9273:Poneratoxin 9263:Ciguatoxins 9150:Raxatrigine 9145:Ralfinamide 9140:PF-05089771 9135:PF-04531083 9107:Analgesics: 9065:Piperocaine 9050:Meprylcaine 9045:Mepivacaine 9000:Cinchocaine 8979:Ropivacaine 8971:Bupivacaine 8898:Sipatrigine 8883:Pheneturide 8878:Phenacemide 8863:Mephenytoin 8848:Lamotrigine 8828:Elpetrigine 8783:Propafenone 8728:Dronedarone 8304:Tolbutamide 8294:Repaglinide 8289:Nateglinide 8284:Mitiglinide 8264:Glisoxepide 8249:Glimepiride 8239:Glicaramide 8219:Carbutamide 8121:Linopirdine 8104:Vernakalant 8094:Tolterodine 8084:Terfenadine 8074:Tamulotoxin 8069:Solifenacin 8039:PNU-282,987 8014:Haloperidol 8009:Gigactonine 7989:Domperidone 7974:Darifenacin 7939:Bedaquiline 7924:Azaspiracid 7887:Vernakalant 7822:Linopirdine 7782:Dronedarone 7772:Dendrotoxin 7757:Clamikalant 7629:Tolperisone 7624:Tetrandrine 7614:Sipatrigine 7609:Silperisone 7594:Prenylamine 7534:Lidoflazine 7489:Elpetrigine 7399:Mirogabalin 7303:Lamotrigine 7298:Flunarizine 7293:Efonidipine 7283:Cinnarizine 7278:Cilnidipine 7233:NNC 55-0396 7159:Ralfinamide 7106:Fantofarone 7101:Dronedarone 7086:Budiodarone 7081:Brinazarone 7044:Levemopamil 6944:Sornidipine 6939:Sagandipine 6929:Pranidipine 6904:Nisoldipine 6894:Nilvadipine 6884:Niguldipine 6874:Nicardipine 6839:Lemildipine 6824:Iganidipine 6819:Furnidipine 6784:Cronidipine 6779:Clevidipine 6774:Barnidipine 6764:Aranidipine 6636:Light-gated 5118:IK channel 4304:(1): 6304. 3635:(1): 5831. 3004:(1): 7–57. 1995:(1): 1416. 1621:Ion channel 1448:neurotensin 1444:Substance P 1386:μ-Conotoxin 1363:veratridine 1196:none known 984:Fibronectin 943:none known 762:, familial 410:Deactivated 376:Inactivated 359:Inactivated 185:Selectivity 51:sodium ions 9765:Categories 9623:Bumetanide 9561:Activators 9551:Piretanide 9546:Lonidamine 9497:Activators 9482:Mibefradil 9477:Mefloquine 9467:Furosemide 9462:Fluoxetine 9442:Crofelemer 9329:Activators 9252:Versutoxin 9248:Robustoxin 9230:Activators 9215:Safinamide 9165:Conotoxins 9100:Trimecaine 9095:Tetracaine 9070:Prilocaine 9060:Orthocaine 9035:Iontocaine 9030:Hexylcaine 9025:Etidocaine 8966:Benzocaine 8956:Amylocaine 8938:Zonisamide 8933:Valpromide 8903:Topiramate 8893:Rufinamide 8853:Lacosamide 8818:Cenobamate 8773:Prajmaline 8763:Moricizine 8758:Mexiletine 8753:Lorcainide 8738:Flecainide 8703:Ranolazine 8643:Activators 8628:Fluoxetine 8572:Nimesulide 8554:-specific: 8540:Activators 8522:-specific: 8474:-specific: 8454:Rilmakalim 8444:Nicorandil 8404:Cromakalim 8391:-specific: 8372:Activators 8362:Tipepidine 8352:Ifenprodil 8327:Caramiphen 8319:-specific: 8299:Tolazamide 8259:Gliquidone 8244:Gliclazide 8211:-specific: 8164:Retigabine 8159:Flupirtine 8156:-specific: 8141:Activators 8118:-specific: 8099:Vanoxerine 8079:Terodiline 8064:Sertindole 8054:Ranolazine 7919:Astemizole 7909:Amiodarone 7877:Terikalant 7852:Pinokalant 7837:Nifekalant 7832:Maurotoxin 7827:Lolitrem B 7817:Kaliotoxin 7777:Dofetilide 7767:Dalazatide 7762:Conotoxins 7732:Amiodarone 7727:Almokalant 7649:Activators 7639:Valperinol 7619:Terodiline 7559:Naftopidil 7549:Mesuximide 7479:Enpiperate 7459:Cycleanine 7444:Bevantolol 7434:Bencyclane 7424:Pregabalin 7414:PD-299,685 7409:PD-217,014 7404:PD-200,347 7394:Imagabalin 7384:Gabapentin 7374:Atagabalin 7364:Arbaclofen 7323:Mibefradil 7318:Loperamide 7313:Lomerizine 7288:Dotarizine 7268:Benidipine 7248:Zonisamide 7164:Safinamide 7139:Caroverine 7091:Celivarone 7039:Gallopamil 6994:Siratiazem 6984:Iprotiazem 6974:Clentiazem 6954:Tiamdipine 6949:Teludipine 6914:Olradipine 6899:Nimodipine 6889:Niludipine 6879:Nifedipine 6869:Mesudipine 6859:Manidipine 6834:Lacidipine 6829:Isradipine 6814:Flordipine 6809:Felodipine 6804:Elnadipine 6799:Elgodipine 6789:Darodipine 6759:Amlodipine 5839:Bestrophin 5097:SK channel 5065:BK channel 4739:γ-subunits 4712:β-subunits 4695:δ-subunits 4426:2008-12-18 3513:(3): e55. 3129:10453/5728 2508:2020-07-16 2044:2009-10-30 2032:Lossin C. 1788:(3): 207. 1644:References 1564:1.3 and Na 1460:G-proteins 1351:delphinine 1346:ciguatoxin 1341:brevetoxin 1314:See also: 1310:Activators 1280:K channels 1255:, further 1000:ectodomain 655:inherited 483:amino acid 466:population 401:Rebounding 311:Polarized 114:change in 45:that form 9744:See also: 9643:Mepacrine 9589:Ivacaftor 9505:Carbachol 9388:Ibuprofen 9378:Amiloride 9337:Solnatide 9309:Amiloride 9238:Aconitine 9200:Evenamide 9175:Saxitoxin 9090:Risocaine 9040:Lidocaine 8985:Butacaine 8961:Articaine 8888:Phenytoin 8798:Tocainide 8793:Sparteine 8788:Quinidine 8748:Lorajmine 8743:Lidocaine 8733:Encainide 8718:Aprindine 8459:Sarakalim 8449:Pinacidil 8439:Naminidil 8429:Minoxidil 8424:Mazokalim 8409:Diazoxide 8399:Bimakalim 8394:Aprikalim 8357:Tertiapin 8337:Clozapine 8254:Glipizide 8049:Quinidine 7999:Ergtoxins 7964:Cisapride 7954:BRL-32872 7934:Azimilide 7897:(KCNH2, K 7872:Tedisamil 7857:Quinidine 7847:Paxilline 7812:Inakalant 7807:Ibutilide 7792:Hanatoxin 7747:Bunaftine 7742:Bretylium 7737:Azimilide 7722:Adekalant 7681:Potassium 7663:Bay K8644 7604:Sesamodil 7554:Monatepil 7544:Manoalide 7539:Magnesium 7524:Imepitoin 7514:Fendiline 7494:Ethadione 7484:Eperisone 7464:Dauricine 7439:Berbamine 7350:δ subunit 7154:PD-173212 7069:Verapamil 7059:Ronipamil 7049:Nexopamil 7034:Falipamil 7029:Etripamil 7014:Devapamil 7009:Dagapamil 6989:Nictiazem 6979:Diltiazem 6969:Diltiazem 6919:Oxodipine 6667:disorders 6665:see also 6448:Cytoplasm 6358:Aquaporin 5827:Anoctamin 5650:11.1/hERG 3886:0920-9964 3829:1531-8257 3772:1537-6605 3716:0896-6273 3657:2041-1723 3591:0960-9822 3529:1545-7885 3470:1097-4199 3410:1469-3178 3349:1476-4687 3283:0092-8674 3221:0014-5793 3074:1097-4199 2265:: 17–25. 1688:cite book 1658:Kandel ER 1609:Chronaxie 1440:verapamil 1331:aconitine 1261:excitable 1141:1.1 to Na 1104:1.5 to Na 1058:1.1 to Na 1020:Gene link 750:Cardiac: 523:Figure 1. 505:Diversity 450:Markovian 384:Undershot 325:Activated 238:conserved 205:Structure 9729:instead. 9704:instead. 9615:Blockers 9607:Unsorted 9533:Blockers 9434:Blockers 9411:Chloride 9373:A-317567 9365:Blockers 9314:Benzamil 9301:Blockers 9130:NKTR-171 9125:GDC-0276 9120:Funapide 9115:DSP-2230 9110:AZD-3161 9075:Procaine 8990:Butamben 8838:Ethotoin 8713:Ajmaline 8692:Blockers 8651:Riluzole 8610:Blockers 8508:Blockers 8414:Emakalim 8192:Blockers 8034:Pimozide 7904:Ajmaline 7704:Blockers 7519:Fostedil 7449:Canadine 7419:Phenibut 7379:Baclofen 7328:NP078585 7273:Bepridil 7111:SR-33805 7064:Tiapamil 7024:Emopamil 7004:Anipamil 6739:Blockers 6461:Connexin 5741:minK/ISK 4385:30362397 4355:Channels 4336:29674667 4244:16873405 4195:23283979 4144:22701426 4093:12181282 3943:29460150 3902:21402201 3894:20889312 3847:24227479 3790:24075186 3732:14910947 3724:16364900 3675:33203861 3599:17350263 3547:18336069 3488:21040849 3428:19575010 3367:19092807 3299:17165089 3291:17448995 3237:26183219 3229:10094463 3179:10491073 3138:11171353 3092:22196327 3028:26671757 2974:11470829 2925:15833746 2825:11567041 2776:21411801 2768:16817858 2732:15282281 2683:15317864 2634:22885909 2626:11389473 2591:11997395 2550:10753953 2438:17928749 2430:10798388 2389:22348792 2338:16075041 2289:27875746 2240:24613995 2190:44433455 2182:22875823 2147:30146301 2096:30672368 2038:Archived 2019:35301303 1961:16382098 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