Sodium channel - Knowledge

414:. 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. 233:, 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. 1529:

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.

508: 222:. 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. 199: 1416: 257:. 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 1516:

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

967:. 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 1506:

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.

170:. 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. 3094:

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).

3999:"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" 620:), intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), Panayiotopoulos syndrome, familial hemiplegic migraine (FHM), familial autism, Rasmussens's encephalitis and Lennox-Gastaut syndrome 2440:

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

538:, 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. 1408:

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

421:. 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. 1848:

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

601: 9641: 8262: 7007: 6952: 6947: 6912: 2687:"Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons" 9123: 8886: 8816: 7745: 7602: 7477: 7221: 7069: 7032: 6932: 6927: 6827: 6812: 6807: 6772: 1248:

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

9143: 8465: 8114: 7211: 4283:"A Mixed Periodic Paralysis & Myotonia Mutant, P1158S, Imparts pH-Sensitivity in Skeletal Muscle Voltage-gated Sodium Channels" 9381: 7334: 6069: 6052: 6047: 6042: 6037: 417:

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

253:, about −70 mV in most human neurons, and Na channels are in their deactivated state, blocked on the extracellular side by their 1926:"International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels" 7231: 7157: 6074: 5172: 4444: 3612:

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

9676: 8166: 3921: 3435:"Extracellular calcium controls background current and neuronal excitability via an UNC79-UNC80-NALCN cation channel complex" 1741: 1708: 1666: 8606: 8584: 6680: 6126: 5307: 2929:"Sodium channel beta1 and beta3 subunits associate with neurofascin through their extracellular immunoglobulin-like domain" 1456: 9764: 8479: 6024: 5045: 2195:"Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome" 3737:"Mutations in NALCN cause an autosomal-recessive syndrome with severe hypotonia, speech impairment, and cognitive delay" 9408: 6713: 5810: 991:

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).

2638:"Contactin associates with sodium channel Nav1.3 in native tissues and increases channel density at the cell surface" 2593:

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

210:, S – ion selectivity, I – inactivation. Positive (+) charges in S4 are important for transmembrane voltage sensing. 7678: 2149:

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

854: 850: 3246:"The Neuronal Channel NALCN Contributes Resting Sodium Permeability and Is Required for Normal Respiratory Rhythm" 2513:"Sodium channel beta subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact" 8369: 8189: 6673: 6403: 5402: 5180: 4496: 3904:

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).

971:(ECM) molecules. Contactin, also known as F3 or F11, associates with beta 1 as shown via co-immunoprecipitation. 705: 3554:"A Putative Cation Channel and Its Novel Regulator: Cross-Species Conservation of Effects on General Anesthesia" 2829:"Interaction of voltage-gated sodium channels with the extracellular matrix molecules tenascin-C and tenascin-R" 1561:

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

163: 6425: 1257: 19: 3794:"Genomewide association study in cervical dystonia demonstrates possible association with sodium leak channel" 1520:

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

80: 9735: 6000: 4912: 188: 112: 2393:"From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels" 2342:"A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia" 9715: 6275: 3492:"A putative cation channel, NCA-1, and a novel protein, UNC-80, transmit neuronal activity in C. elegans" 410: 987:-like (EGF-like) repeats that repel beta2. A disintegrin and metalloproteinase (ADAM) 10 sheds beta 2's 467: 9759: 4453: 4437: 1860:

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.

792: 31: 3947:"Effects of external protons on single cardiac sodium channels from guinea pig ventricular myocytes" 3679:"The Ion Channel Narrow Abdomen Is Critical for Neural Output of the Drosophila Circadian Pacemaker" 2242:

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).

1974:"Structure-guided unlocking of NaX reveals a non-selective tetrodotoxin-sensitive cation channel" 984: 226: 4048:"Role of outer ring carboxylates of the rat skeletal muscle sodium channel pore in proton block" 1815:

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

9353: 9289: 8680: 7646: 7637: 7201: 7188: 7170: 7112: 6736: 6655: 4647: 4634: 4621: 4601: 4588: 4553: 1517: 1293: 1253: 1207: 900: 876: 709: 587: 454: 3375:"The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic beta-cell line" 1161: 1120: 1075: 1037: 923: 827: 781: 730: 694: 670: 635: 581: 9317: 9218: 4430: 4097:"Acidosis differentially modulates inactivation in na(v)1.2, na(v)1.4, and na(v)1.5 channels" 3186:"Cloning of a novel four repeat protein related to voltage-gated sodium and calcium channels" 1489:

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

446: 438: 4298: 3629: 3321: 2844: 2554:"Structural requirements for interaction of sodium channel beta 1 subunits with ankyrin" 2454: 7972: 7967: 7870: 7577: 7347: 5995: 4871: 4518: 4364: 4339: 4315: 4282: 4223: 4198: 4174: 4147: 4123: 4096: 4072: 4047: 4023: 3998: 3971: 3946: 3886: 3826: 3793: 3769: 3736: 3716: 3654: 3613: 3591: 3526: 3491: 3467: 3434: 3407: 3374: 3346: 3305: 3283: 3221: 3071: 3038: 3007: 2982: 2953: 2928: 2804: 2795: 2779: 2760: 2711: 2686: 2662: 2637: 2618: 2422: 2368: 2341: 2317: 2292: 2268: 2243: 2219: 2194: 2174: 2126: 2099: 1998: 1973: 1953: 1903: 1676: 1237: 104: 3201: 2409: 2392: 1793: 1766: 1573:

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".

1591: 846: 700: 645: 605: 207: 4259: 2244:"De novo and inherited SCN8A epilepsy mutations detected by gene panel analysis" 2100:"V1.3) Regulation of Human Cerebral Cortical Folding and Oral Motor Development" 1733: 1557:

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

1256:. The ability of these channels to assume a closed-inactivated state causes the 9626: 9582: 9173: 9073: 8983: 8513: 8456: 8301: 8257: 8212: 7957: 7947: 7567: 7487: 7084: 6987: 6134: 4306: 4148:"Proton sensors in the pore domain of the cardiac voltage-gated sodium channel" 3752: 3637: 3262: 3245: 2833:

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

2075: 2058: 1989: 1891: 1646: 1384: 1245: 1240:, a small but significant number of Na ions will move into the cell down their 549:

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

478:. The cations flow into a more constricted part of the pore that is 0.3 by 0.5 147: 43: 7117: 6712: 3570: 3553: 1374: 1348:, e.g., grayanotoxin I (other granotoxins inactive, or close, sodium channels) 998:

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

9753: 9636: 9529: 9475: 9460: 9246: 9183: 8916: 8861: 8856: 8846: 8801: 8621: 8555: 8407: 8217: 8202: 8047: 7740: 7622: 7462: 7342: 7321: 7296: 7216: 6837: 6832: 6088: 5761: 4199:"Isoform-dependent interaction of voltage-gated sodium channels with protons" 4113: 3874: 3817: 3760: 3704: 3645: 3579: 3517: 3458: 3398: 3337: 3271: 3209: 3062: 2983:"Brugada Syndrome: Clinical, Genetic, Molecular, Cellular, and Ionic Aspects" 2853: 2529: 2512: 1861: 1452: 1451:) which in turn increase the permeability of NALCN through UNC80 activation. 1345: 1324: 1215: 1020: 953: 837: 564: 203: 46: 6121: 6019: 4164: 2462: 2358: 1849: 1783: 9508: 9256: 9168: 9158: 9068: 9003: 8901: 8831: 8766: 8756: 8711: 8335: 8320: 8267: 8222: 8077: 8032: 8017: 8007: 7992: 7932: 7572: 7552: 7492: 7042: 6897: 6757: 6441: 5832: 4373: 4324: 4232: 4183: 4132: 4081: 3931: 3882: 3835: 3778: 3712: 3663: 3587: 3535: 3476: 3416: 3390: 3355: 3279: 3217: 3167: 3126: 3080: 3016: 2962: 2913: 2904: 2887: 2813: 2756: 2720: 2671: 2614: 2579: 2570: 2553: 2538: 2418: 2377: 2326: 2277: 2228: 2170: 2135: 2084: 2007: 1949: 1899: 1802: 1751: 1696: 1424: 1196: 956: 858: 507: 4267: 4032: 4014: 3980: 3962: 3908:. Handbook of Experimental Pharmacology. Vol. 246. pp. 147–160. 3614:"Structure of the human sodium leak channel NALCN in complex with FAM155A" 3108: 2944: 2872: 2470: 1837: 1825: 1271:, producing an influx of positive charge (Na) toward the beginning of the 9307: 9261: 9138: 9133: 9128: 9053: 9038: 9033: 8988: 8967: 8959: 8871: 8866: 8851: 8836: 8771: 8716: 8292: 8282: 8277: 8272: 8252: 8237: 8227: 8207: 8109: 8092: 8082: 8072: 8062: 8057: 8027: 8002: 7997: 7977: 7962: 7927: 7912: 7875: 7810: 7770: 7760: 7617: 7612: 7597: 7582: 7522: 7387: 7291: 7286: 7281: 7271: 7266: 7147: 7094: 7089: 7074: 6917: 6892: 6882: 6872: 6862: 6852: 6767: 6762: 6752: 6665: 6371: 6366: 6361: 6356: 6243: 6082: 4457: 1728:. Metal Ions in Life Sciences. Vol. 16. Springer. pp. 325–347. 1609: 1436: 1432: 1351: 972: 514:

Likely evolutionary relationship of the nine known human sodium channels.

39: 35: 4407:. International Union of Basic and Clinical Pharmacology. Archived from 3913: 3329: 445:-type formalism. In the former scheme, each channel occupies a distinct 249:

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

9611: 9539: 9534: 9470: 9465: 9455: 9450: 9430: 9251: 9240: 9236: 9203: 9088: 9083: 9058: 9048: 9023: 9018: 9013: 8954: 8944: 8926: 8921: 8891: 8881: 8841: 8806: 8761: 8751: 8746: 8741: 8726: 8691: 8616: 8560: 8537: 8505: 8432: 8392: 8350: 8340: 8315: 8287: 8247: 8232: 8152: 8147: 8087: 8067: 8052: 8042: 7907: 7897: 7825: 7820: 7815: 7805: 7765: 7720: 7715: 7627: 7607: 7547: 7537: 7467: 7447: 7432: 7422: 7412: 7397: 7382: 7372: 7362: 7352: 7311: 7306: 7301: 7276: 7256: 7236: 7162: 7152: 7137: 7127: 7079: 7027: 6962: 6887: 6877: 6867: 6847: 6822: 6817: 6797: 6777: 6747: 6351: 5717: 5085: 5053: 3093: 2339: 2293:"Sodium channel mutations in epilepsy and other neurological disorders" 1423:

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

1339: 1334: 1329: 988: 482:

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

471: 4146:

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

3906:

Voltage-gated Sodium Channels: Structure, Function and Channelopathies

3809: 3117: 3039:"Sodium leak channels in neuronal excitability and rhythmic behaviors" 2551: 1941: 929:

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

9631: 9577: 9493: 9376: 9366: 9297: 9226: 9188: 9163: 9153: 9078: 9028: 8973: 8949: 8876: 8786: 8781: 8776: 8736: 8731: 8721: 8706: 8565: 8437: 8417: 8397: 8387: 8345: 8325: 8242: 8037: 7952: 7942: 7922: 7860: 7845: 7835: 7795: 7780: 7750: 7735: 7730: 7725: 7651: 7592: 7542: 7532: 7527: 7512: 7502: 7482: 7472: 7452: 7427: 7057: 7022: 7002: 6967: 6957: 6922: 6907: 6436: 6346: 2606: 2308: 1597: 1532: 1448: 1428: 1319: 487: 479: 4452: 2777: 2057:

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

429:, which can cause muscle and/or nerve cells to become over-excited. 9302: 9108: 9103: 9063: 8978: 8826: 8701: 8639: 8022: 7987: 7892: 7507: 7437: 7407: 7367: 7261: 7052: 7012: 6992: 6449: 5797: 4776: 4771: 4766: 4761: 4693: 4688: 3184:

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

2926: 2886:

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

1313: 980: 976: 964: 947: 806: 798: 649: 597: 483: 475: 4197:

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

4046:

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

2927:

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

2510: 2241: 2014: 1644: 9371: 9193: 8993: 8518: 7917: 7855: 7517: 7497: 7193: 7064: 6576: 6333: 6169: 4670: 4665: 4660: 3140:

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

2511:

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

1415: 1368: 1260:

and is critical for the propagation of action potentials down an

1054:

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

960: 198: 3733: 9197: 8461:

Tooltip G protein-coupled inwardly rectifying potassium channel

8310: 8306:

Tooltip G protein-coupled inwardly rectifying potassium channel

7982: 7902: 7785: 7775: 7557: 7326: 6253: 6248: 5982: 5977: 5923: 5918: 5734: 5722: 5712: 5707: 5695: 5690: 5685: 5572: 5567: 5562: 5454: 5390: 5385: 5380: 5375: 5370: 5365: 5360: 5295: 5290: 5280: 5275: 5270: 5221: 5216: 5206: 5201: 5078: 5073: 5068: 5063: 4969: 4964: 4959: 4949: 4944: 4934: 4929: 4859: 4854: 4849: 4844: 4747: 4742: 4737: 4732: 4720: 4715: 4710: 4705: 4614: 4581: 4576: 4571: 4566: 3139: 1236:. If enough channels open when there is a change in the cell's 890: 866: 817: 810: 802: 720: 684: 625: 612:

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

571: 520: 155: 151: 121: 4281:

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

4280: 9677: 8167: 7937: 7790: 6487: 6418: 6413: 6408: 6325: 6312: 6307: 6302: 6297: 6292: 6287: 6238: 6231: 6226: 6221: 6216: 6211: 6206: 6201: 6196: 6184: 6179: 6174: 6164: 6159: 6154: 6149: 6064: 6008: 5965: 5960: 5955: 5950: 5945: 5940: 5935: 5913: 5908: 5903: 5898: 5893: 5888: 5883: 5864: 5859: 5854: 5849: 5837: 5754: 5749: 5744: 5729: 5667: 5662: 5657: 5648: 5643: 5629: 5624: 5615: 5610: 5605: 5596: 5591: 5582: 5577: 5544: 5539: 5534: 5529: 5520: 5511: 5506: 5501: 5492: 5487: 5482: 5477: 5468: 5463: 5449: 5444: 5439: 5434: 5429: 5424: 5419: 5355: 5350: 5345: 5340: 5335: 5330: 5325: 5320: 5285: 5255: 5250: 5245: 5240: 5211: 5160: 5155: 5150: 5145: 5135: 5130: 5110: 5095: 5090: 5005: 5000: 4995: 4990: 4974: 4954: 4939: 4900: 4895: 4890: 4885: 4793: 4788: 4511: 4506: 4501: 3371: 2059:"The Role of Voltage-Gated Sodium Channels in Pain Signaling" 1151: 1110: 1065: 1027: 914: 771: 660: 202:

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

8585: 3903: 3849:

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

3791: 2826: 9513:

Tooltip Cystic fibrosis transmembrane conductance regulator

9435: 8480: 8138: 8100: 7883: 6567: 6562: 6557: 6547: 6542: 6537: 6527: 6522: 6517: 6512: 6507: 6502: 6497: 6482: 6477: 6472: 6467: 6462: 6457: 6396: 6391: 6386: 6381: 6376: 6282: 6270: 6265: 6260: 6191: 6144: 6108: 6103: 6098: 6093: 5820: 5638: 5196: 4533: 4523: 3997:

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

3551: 1594: – Ion channel complex through which calcium ions pass 1419:

Regulatory pathways and chemicals affecting NALCN function.

1364:

The following toxins modify the gating of sodium channels:

1261: 159: 9409: 6714: 3996: 2684: 1970: 1703:(3rd ed.). Sunderland, Mass: Sinauer. pp. 73–7. 1141:

central neurons, adrenal gland, kidney, peripheral neurons

5140: 5100: 2827:

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

2191: 2022: 1523: 437:

The temporal behavior of Na channels can be modeled by a

7679: 4145: 4045: 2885: 2733: 1537:

The effects of protonation have been characterized in Na

1402: 1232:

Voltage-gated sodium channels play an important role in

676:

Central neurons, peripheral neurons and cardiac myocytes

8370: 8190: 2439: 2056: 1620:

Pages displaying short descriptions of redirect targets

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

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heart, skeletal muscle, central and peripheral neurons

8667: 2980: 1923: 1767:"Overview of the voltage-gated sodium channel family" 16:

Transmembrane protein allowing sodium ions in and out

4337: 4196: 3183: 2097: 1924:

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

4338:Ghovanloo MR, Peters CH, Ruben PC (October 2018). 3676: 3489: 2635: 1650: 1533:pH modulation across the subtypes studied thus far 1427:. NALCN is blocked nonspecifically by both Gd and 1267:Na channels both open and close more quickly than 9702: 9276: 2592: 2148: 1476:the axon, and contributes to membrane stability. 432: 9751: 9340: 6610: 4094: 1689: 1657:(4th ed.). New York: McGraw-Hill. pp. 1638: 1100:Central Neurons, peripheral neurons, heart, glia 948:Role of beta subunits as cell adhesion molecules 218:that associate with accessory proteins, such as 182: 9740:Transient receptor potential channel modulators 3944: 3432: 1191: 461: 4245: 3992: 3990: 2290: 1393: 1199:sodium channels are activated by binding of a 855:channelopathy-associated insensitivity to pain 9682:Tooltip Transient receptor potential channels 8172:Tooltip Inwardly rectifying potassium channel 6681: 4438: 4405:IUPHAR Database of Receptors and Ion Channels 3848: 3087: 1695: 1569:1.4, but steady-state fast inactivation in Na 8590:Tooltip Tandem pore domain potassium channel 4274: 4190: 4139: 4088: 4039: 3897: 3133: 2981:Antzelevitch C, Patocskai B (January 2016). 2920: 2879: 2771: 2727: 2678: 2629: 2586: 2545: 2504: 2384: 2333: 2185: 1919: 1917: 1681:: CS1 maint: multiple names: authors list ( 857:and recently discovered a disabling form of 8488:Tooltip Calcium-activated potassium channel 4239: 3987: 3938: 3303: 3142:"Scorpion toxins specific for Na+-channels" 2820: 2433: 1764: 1581:1.5 is the most proton-sensitive subtypes. 1282: 1221: 1203:instead of a change in membrane potential. 526:The proteins of these channels are named Na 9414:Tooltip Calcium-activated chloride channel 7706:4-Aminopyridine (fampridine/dalfampridine) 6719:Tooltip Voltage-dependent calcium channels 6695: 6688: 6674: 4445: 4431: 3611: 3243: 1862:https://doi.org/10.1016/j.cell.2017.06.039 162:, sodium channels are responsible for the 5029: 4474: 4392:at the U.S. National Library of Medicine 4363: 4314: 4222: 4173: 4163: 4122: 4112: 4071: 4022: 3970: 3945:Zhang JF, Siegelbaum SA (December 1991). 3825: 3768: 3694: 3653: 3569: 3525: 3507: 3466: 3406: 3345: 3261: 3157: 3116: 3070: 3006: 2952: 2903: 2862: 2852: 2803: 2710: 2661: 2569: 2528: 2408: 2390: 2367: 2357: 2316: 2267: 2218: 2125: 2115: 2074: 1997: 1914: 1850:https://doi.org/10.1016/j.bpj.2021.12.025 1792: 1782: 1726:The Alkali Metal Ions: Their Role in Life 1455:can also increase NALCN activity through 107:, which is also called change in voltage 7684:Tooltip Voltage-gated potassium channels 1723: 1414: 506: 197: 18: 8378:Tooltip ATP-sensitive potassium channel 8198:Tooltip ATP-sensitive potassium channel 6598: 4817: 1964: 1873: 1871: 1869: 1838:https://doi.org/10.1073/pnas.1814928115 983:-R bind with beta 2 in contrast to the 466:The pore of sodium channels contains a 9752: 4095:Vilin YY, Peters CH, Ruben PC (2012). 2291:Meisler MH, Kearney JA (August 2005). 1826:http://dx.doi.org/10.1085/jgp.69.4.497 1524:pH modulation of sodium channel gating 1479: 749:progressive cardiac conduction disease 8672:Tooltip Voltage-gated sodium channels 6669: 6597: 5782: 5028: 4816: 4473: 4426: 3607: 3605: 3547: 3545: 3428: 3426: 3367: 3365: 3299: 3297: 3239: 3237: 3235: 3179: 3177: 3032: 3030: 3028: 3026: 2976: 2974: 2972: 2297:The Journal of Clinical Investigation 2052: 2050: 2048: 2046: 1612: – Pore-forming membrane protein 1403:Structural and functional differences 75:(factor that stimulates the channel) 8607:12-O-Tetradecanoylphorbol-13-acetate 2737:The European Journal of Neuroscience 2020: 1877: 1866: 1511:Molecular mechanisms of proton block 1492: 679:epilepsy, pain, brain malformations 7701:3,4-Diaminopyridine (amifampridine) 5811:Calcium-activated chloride channels 4152:The Journal of Biological Chemistry 3097:The Journal of Experimental Biology 3036: 2892:The Journal of Biological Chemistry 2558:The Journal of Biological Chemistry 2517:The Journal of Biological Chemistry 1701:Ion Channels of Excitable Membranes 1618: – Class of transport proteins 1359: 641:Central neurons, peripheral neurons 610:severe myclonic epilepsy of infancy 215: 13: 4881:Amiloride-sensitive cation channel 3741:American Journal of Human Genetics 3602: 3542: 3423: 3362: 3294: 3232: 3174: 3023: 2969: 2796:10.1523/JNEUROSCI.21-19-07517.2001 2043: 1627: – Use of sodium by organisms 1606: – Group of membrane proteins 1470: 1461:muscarinic acetylcholine receptors 1275:and an efflux (K) toward the end. 219: 61:They are classified into 2 types: 14: 9781: 9707:Tooltip Ligand gated ion channels 9281:Tooltip Epithelial sodium channel 5783: 4383: 4003:The Journal of General Physiology 3951:The Journal of General Physiology 1758: 885:pain, neuropsychiatric disorders 616:), Doose syndrome (also known as 542:is summarized in table 1, below. 502: 214:Sodium channels consist of large 56: 9345:Tooltip Acid-sensing ion channel 3159:10.1046/j.1432-1327.1999.00625.x 3146:European Journal of Biochemistry 2749:10.1111/j.1460-9568.2006.04789.x 2260:10.1016/j.eplepsyres.2016.11.002 1600: – Electrophysiology metric 1501: 938: 6404:Voltage-dependent anion channel 4497:Inositol trisphosphate receptor 4401:"Voltage-Gated Sodium Channels" 4331: 3842: 3785: 3727: 3670: 3483: 2999:10.1016/j.cpcardiol.2015.06.002 2485:"Blackboard Server Unavailable" 2477: 2284: 2235: 2142: 2091: 2029:from the original on 2011-07-21 706:hyperkalemic periodic paralysis 7163:Ziconotide (ω-conotoxin MVIIA) 6426:General bacterial porin family 2987:Current Problems in Cardiology 2703:10.1523/JNEUROSCI.1628-04.2004 2654:10.1523/JNEUROSCI.0322-04.2004 1854: 1842: 1830: 1818: 1809: 1717: 490:residues that line the pore. 433:Modeling the behavior of gates 183:Voltage-gated sodium channels 173: 120:binding of substances such as 51:superfamily of cation channels 1: 9736:Receptor/signaling modulators 7138:Leconotide (ω-conotoxin CVID) 4356:10.1080/19336950.2018.1539611 4248:Journal of Applied Physiology 3202:10.1016/S0014-5793(99)00082-4 2410:10.1016/S0896-6273(00)81133-2 2346:BMC Musculoskeletal Disorders 1632: 1545:1.5. Among these channels, Na 1410:voltage-gated calcium channel 1298: 1192:Ligand-gated sodium channels 714:potassium-aggravated myotonia 385:Repolarized → Hyperpolarized 81:Voltage-gated sodium channels 4215:10.1113/jphysiol.2006.115659 4064:10.1113/jphysiol.2002.021014 3867:10.1016/j.schres.2010.09.002 3696:10.1016/j.neuron.2005.10.030 3509:10.1371/journal.pbio.0060055 3451:10.1016/j.neuron.2010.09.014 3055:10.1016/j.neuron.2011.12.007 2595:Nature Reviews. Neuroscience 2211:10.1053/j.gastro.2014.02.054 2163:10.1136/heartjnl-2012-301784 2117:10.1016/j.neuron.2018.07.052 1765:Yu FH, Catterall WA (2003). 1653:Principles of Neural Science 1447:(independent of the coupled 1206:They are found, e.g. in the 493: 462:Impermeability to other ions 193: 189:voltage-gated sodium channel 113:ligand-gated sodium channels 7: 4260:10.1152/jappl.1972.32.3.304 2933:The Journal of Cell Biology 2784:The Journal of Neuroscience 2691:The Journal of Neuroscience 2642:The Journal of Neuroscience 2391:Catterall WA (April 2000). 1734:10.1007/978-3-319-21756-7_9 1584: 1394:Sodium leak channel (NALCN) 1287: 975:-like (FN-like) repeats of 470:made of negatively charged 402:Hyperpolarized → Polarized 141: 10: 9786: 9765:Integral membrane proteins 8699:Antiarrhythmics (class I): 5845:Chloride Channel Accessory 4454:Membrane transport protein 4307:10.1038/s41598-018-24719-y 3753:10.1016/j.ajhg.2013.08.001 3638:10.1038/s41467-020-19667-z 3263:10.1016/j.cell.2007.02.041 3037:Ren, Dejian (2011-12-22). 2076:10.1152/physrev.00052.2017 1990:10.1038/s41467-022-28984-4 1892:10.1177/107385840100700108 1486:resting membrane potential 1302: 1291: 1225: 618:myoclonic astatic epilepsy 351:Depolarized → Repolarized 186: 32:integral membrane proteins 9729: 9700: 9675: 9668: 9602: 9595: 9548: 9520: 9506: 9484: 9421: 9407: 9398: 9352: 9338: 9316: 9288: 9274: 9217: 9209:Tricyclic antidepressants 8679: 8665: 8656: 8630: 8597: 8583: 8527: 8495: 8478: 8359: 8218:Glibenclamide (glyburide) 8179: 8165: 8128: 7691: 7677: 7668: 7636: 6726: 6703: 6651: 6606: 6593: 6434: 6323: 6119: 6017: 5993: 5795: 5791: 5778: 5401: 5306: 5171: 5044: 5040: 5024: 4911: 4870: 4840:Epithelial sodium channel 4832: 4828: 4812: 4544: 4489: 4485: 4469: 4203:The Journal of Physiology 4101:Frontiers in Pharmacology 4052:The Journal of Physiology 3571:10.1016/j.cub.2007.02.037 1604:Epithelial sodium channel 1443:through their respective 1279:excitability) of a cell. 861:(rs6754031 polymorphism) 382:Inactivated → Deactivated 240: 4757:Cation channels of sperm 4394:Medical Subject Headings 4114:10.3389/fphar.2012.00109 2854:10.1073/pnas.95.26.15753 2530:10.1074/jbc.275.15.11383 2193:Farrugia G (June 2014). 1283:Pharmacologic modulation 1242:electrochemical gradient 1222:Role in action potential 1214:, where the ligands are 763:Irritable bowel syndrome 757:ventricular fibrillation 654:autism spectrum disorder 317:Polarized → Depolarized 23:C is the sodium channel 8822:Eslicarbazepine acetate 4165:10.1074/jbc.M112.434266 2463:10.1126/science.1375395 2359:10.1186/1471-2474-13-23 1930:Pharmacological Reviews 1784:10.1186/gb-2003-4-3-207 1577:1.4 is the least and Na 985:Epidermal growth factor 836:, sympathetic neurons, 331:Activated → Inactivated 297:Deactivated → Activated 158:, and certain types of 8566:Rottlerin (mallotoxin) 6697:Ion channel modulators 3855:Schizophrenia Research 3391:10.1038/embor.2009.125 2905:10.1074/jbc.M412938200 2571:10.1074/jbc.M202354200 1649:, Schwartz JH (2000). 1518:cardiac sodium channel 1467:which inhibits UNC80. 1420: 1294:Sodium channel blocker 1254:positive feedback loop 1208:neuromuscular junction 710:paramyotonia congenita 515: 451:differential equations 283:Neuron's Target State 211: 67:Type of sodium channel 24: 6923:Ryodipine (riodipine) 4833:Constitutively active 4015:10.1085/jgp.110.6.693 3963:10.1085/jgp.98.6.1065 3618:Nature Communications 3109:10.1242/jeb.204.4.711 2945:10.1083/jcb.200102086 2063:Physiological Reviews 1978:Nature Communications 1418: 1305:Sodium channel opener 510: 231:transmembrane voltage 201: 135:Ungated, always open 49:. They belong to the 22: 8912:Valproate semisodium 7443:Carboxyamidotriazole 7378:Gabapentin enacarbil 7358:Arbaclofen placarbil 969:extracellular matrix 842:neuroendocrine cells 129:Leak sodium channel 9563:1,10-Phenanthroline 8120:Spooky toxin (SsTx) 7105:Tetrahydropalmatine 6600:By gating mechanism 4299:2018NatSR...8.6304G 3914:10.1007/164_2018_99 3630:2020NatCo..11.5831X 3330:10.1038/nature07579 3322:2009Natur.457..741L 2845:1998PNAS...9515753S 2455:1992Sci...256..839I 1616:Resting ion channel 1480:Biological function 1212:nicotinic receptors 999: 906:Dorsal root ganglia 882:Dorsal root ganglia 834:Dorsal root ganglia 795:, heart, glia cells 789:dorsal root ganglia 753:atrial fibrillation 550: 280:Gate's Target State 94:"voltage-sensitive" 91:"voltage-dependent" 9573:7,8-Benzoquinoline 9568:4,7-Phenanthroline 9558:1,7-Phenanthroline 8934:Local anesthetics: 8466:ML-297 (VU0456810) 7973:Diallyl trisulfide 7968:Dextropropoxyphene 7871:Tetraethylammonium 7578:Pinaverium bromide 7348:4-Methylpregabalin 6127:TRP cation channel 6025:CNG cation channel 5308:Tandem pore domain 4519:Ryanodine receptor 4287:Scientific Reports 3798:Movement Disorders 2492:blackboard.jhu.edu 1880:The Neuroscientist 1441:Src family kinases 1421: 1238:membrane potential 1057:epilepsy (GEFS+), 1016:Expression profile 994: 793:peripheral neurons 761:Gastrointestinal: 560:Expression profile 545: 516: 468:selectivity filter 411:inactivation gates 274:Membrane Potential 212: 105:membrane potential 25: 9760:Electrophysiology 9747: 9746: 9725: 9724: 9664: 9663: 9660: 9659: 9622:Meclofenamic acid 9591: 9590: 9502: 9501: 9394: 9393: 9390: 9389: 9334: 9333: 9270: 9269: 9144:RG7893 (GDC-0287) 8907:Valproate pivoxil 8797:Acetylpheneturide 8652: 8651: 8648: 8647: 8579: 8578: 8551:Meclofenamic acid 8514:Ethanol (alcohol) 8474: 8473: 8423:Minoxidil sulfate 8161: 8160: 7664: 7663: 7660: 7659: 7563:Otilonium bromide 7488:Ethanol (alcohol) 7252:ω-Conotoxin MVIIC 6988:Phenylalkylamines 6663: 6662: 6647: 6646: 6643: 6642: 6635:Stretch-activated 6612:Ion channel class 6589: 6588: 6585: 6584: 5774: 5773: 5770: 5769: 5046:Calcium-activated 5034:Potassium channel 5020: 5019: 5016: 5015: 4808: 4807: 4804: 4803: 4209:(Pt 2): 493–501. 3923:978-3-319-90283-8 3810:10.1002/mds.25732 3316:(7230): 741–744. 2248:Epilepsy Research 2110:(5): 905–913.e7. 1942:10.1124/pr.57.4.4 1743:978-3-319-21755-0 1710:978-0-87893-321-1 1668:978-0-8385-7701-1 1625:Sodium in biology 1493:Role in pathology 1258:refractory period 1234:action potentials 1189: 1188: 1019:Associated human 936: 935: 787:Central neurons, 563:Associated human 458:Markovian model. 441:scheme or by the 406: 405: 251:resting potential 168:action potentials 139: 138: 9777: 9708: 9704: 9683: 9679: 9673: 9672: 9600: 9599: 9518: 9517: 9514: 9510: 9419: 9418: 9415: 9411: 9405: 9404: 9350: 9349: 9346: 9342: 9286: 9285: 9282: 9278: 8897:Sodium valproate 8812:Chlorphenacemide 8794:Anticonvulsants: 8677: 8676: 8673: 8669: 8663: 8662: 8612:Arachidonic acid 8595: 8594: 8591: 8587: 8493: 8492: 8489: 8485: 8462: 8458: 8379: 8375: 8331:Dextromethorphan 8307: 8303: 8199: 8195: 8177: 8176: 8173: 8169: 7689: 7688: 7685: 7681: 7675: 7674: 7647:L-type-selective 7458:Dimeditiapramine 7420:Others/unsorted: 7202:T-type-selective 7189:R-type-selective 7171:P-type-selective 7123:ω-Conotoxin GVIA 7113:N-type-selective 6743:Dihydropyridines 6737:L-type-selective 6724: 6723: 6720: 6716: 6710: 6709: 6690: 6683: 6676: 6667: 6666: 6608: 6607: 6595: 6594: 5803:Chloride channel 5793: 5792: 5780: 5779: 5173:Inward-rectifier 5042: 5041: 5026: 5025: 4830: 4829: 4814: 4813: 4784:Two-pore channel 4487: 4486: 4471: 4470: 4447: 4440: 4433: 4424: 4423: 4419: 4417: 4416: 4378: 4377: 4367: 4335: 4329: 4328: 4318: 4278: 4272: 4271: 4243: 4237: 4236: 4226: 4194: 4188: 4187: 4177: 4167: 4143: 4137: 4136: 4126: 4116: 4092: 4086: 4085: 4075: 4043: 4037: 4036: 4026: 3994: 3985: 3984: 3974: 3942: 3936: 3935: 3901: 3895: 3894: 3846: 3840: 3839: 3829: 3789: 3783: 3782: 3772: 3731: 3725: 3724: 3698: 3674: 3668: 3667: 3657: 3609: 3600: 3599: 3573: 3549: 3540: 3539: 3529: 3511: 3487: 3481: 3480: 3470: 3430: 3421: 3420: 3410: 3369: 3360: 3359: 3349: 3301: 3292: 3291: 3265: 3241: 3230: 3229: 3196:(2–3): 231–236. 3181: 3172: 3171: 3161: 3137: 3131: 3130: 3120: 3103:(Pt 4): 711–21. 3091: 3085: 3084: 3074: 3034: 3021: 3020: 3010: 2978: 2967: 2966: 2956: 2924: 2918: 2917: 2907: 2898:(24): 23251–61. 2883: 2877: 2876: 2866: 2856: 2824: 2818: 2817: 2807: 2775: 2769: 2768: 2731: 2725: 2724: 2714: 2682: 2676: 2675: 2665: 2633: 2627: 2626: 2607:10.1038/35077553 2590: 2584: 2583: 2573: 2549: 2543: 2542: 2532: 2508: 2502: 2501: 2499: 2498: 2489: 2481: 2475: 2474: 2449:(5058): 839–42. 2437: 2431: 2430: 2412: 2388: 2382: 2381: 2371: 2361: 2337: 2331: 2330: 2320: 2309:10.1172/JCI25466 2288: 2282: 2281: 2271: 2239: 2233: 2232: 2222: 2205:(7): 1659–1668. 2199:Gastroenterology 2189: 2183: 2182: 2146: 2140: 2139: 2129: 2119: 2095: 2089: 2088: 2078: 2069:(2): 1079–1151. 2054: 2041: 2040: 2035: 2034: 2023:"SCN1A infobase" 2018: 2012: 2011: 2001: 1968: 1962: 1961: 1921: 1912: 1911: 1875: 1864: 1858: 1852: 1846: 1840: 1834: 1828: 1822: 1816: 1813: 1807: 1806: 1796: 1786: 1762: 1756: 1755: 1721: 1715: 1714: 1693: 1687: 1686: 1680: 1672: 1656: 1642: 1621: 1360:Gating modifiers 1273:action potential 1228:Action potential 1145:Brugada syndrome 1104:Brugada syndrome 1059:Brugada syndrome 1000: 993: 745:Brugada syndrome 741:Long QT syndrome 646:febrile seizures 614:infantile spasms 592:cardiac myocytes 551: 544: 277:Target Potential 271:Action Potential 268: 267: 255:activation gates 64: 63: 9785: 9784: 9780: 9779: 9778: 9776: 9775: 9774: 9770:Sodium channels 9750: 9749: 9748: 9743: 9721: 9706: 9696: 9681: 9656: 9652:Trifluoperazine 9647:Tolfenamic acid 9617:Flufenamic acid 9587: 9544: 9512: 9498: 9480: 9446:Flufenamic acid 9441:Ethacrynic acid 9413: 9386: 9344: 9330: 9312: 9280: 9266: 9213: 9044:Metabutoxycaine 9009:Diphenhydramine 8999:Cyclomethycaine 8964:Levobupivacaine 8671: 8644: 8626: 8589: 8575: 8571:Tolfenamic acid 8546:Flufenamic acid 8541: 8523: 8509: 8487: 8484: 8470: 8460: 8377: 8374: 8355: 8305: 8197: 8194: 8171: 8157: 8142: 8124: 8104: 8013:Norpropoxyphene 7890:11.1)-specific: 7889: 7683: 7656: 7632: 7588:Rhynchophylline 7338: 6718: 6699: 6694: 6664: 6659: 6639: 6602: 6581: 6430: 6329: 6319: 6115: 6013: 5989: 5787: 5766: 5680: 5557: 5414: 5397: 5302: 5266: 5236: 5192: 5184: 5167: 5121: 5036: 5012: 4985: 4924: 4907: 4866: 4824: 4800: 4683: 4655: 4642: 4629: 4609: 4596: 4561: 4540: 4481: 4479:Calcium channel 4465: 4451: 4414: 4412: 4399: 4390:Sodium+Channels 4386: 4381: 4336: 4332: 4279: 4275: 4244: 4240: 4195: 4191: 4144: 4140: 4093: 4089: 4058:(Pt 1): 71–84. 4044: 4040: 3995: 3988: 3943: 3939: 3924: 3902: 3898: 3847: 3843: 3790: 3786: 3732: 3728: 3675: 3671: 3610: 3603: 3558:Current Biology 3550: 3543: 3488: 3484: 3431: 3424: 3370: 3363: 3302: 3295: 3242: 3233: 3182: 3175: 3138: 3134: 3092: 3088: 3035: 3024: 2979: 2970: 2925: 2921: 2884: 2880: 2839:(26): 15753–7. 2825: 2821: 2790:(19): 7517–25. 2776: 2772: 2743:(10): 2551–62. 2732: 2728: 2697:(30): 6765–75. 2683: 2679: 2648:(33): 7387–99. 2634: 2630: 2591: 2587: 2564:(29): 26681–8. 2550: 2546: 2523:(15): 11383–8. 2509: 2505: 2496: 2494: 2487: 2483: 2482: 2478: 2438: 2434: 2389: 2385: 2338: 2334: 2289: 2285: 2240: 2236: 2190: 2186: 2157:(17): 1318–24. 2147: 2143: 2096: 2092: 2055: 2044: 2032: 2030: 2019: 2015: 1969: 1965: 1922: 1915: 1876: 1867: 1859: 1855: 1847: 1843: 1835: 1831: 1823: 1819: 1814: 1810: 1763: 1759: 1744: 1722: 1718: 1711: 1694: 1690: 1674: 1673: 1669: 1643: 1639: 1635: 1630: 1619: 1592:Calcium channel 1587: 1580: 1576: 1572: 1568: 1564: 1560: 1556: 1552: 1548: 1544: 1540: 1535: 1526: 1513: 1504: 1495: 1482: 1473: 1471:Protein Complex 1460: 1405: 1396: 1362: 1307: 1301: 1296: 1290: 1285: 1230: 1224: 1194: 1178: 1174: 1170: 1155: 1137: 1133: 1129: 1114: 1096: 1092: 1088: 1084: 1069: 1050: 1046: 1031: 1021:channelopathies 950: 941: 918: 894: 870: 847:erythromelalgia 821: 775: 755:and idiopathic 724: 701:Skeletal muscle 688: 664: 629: 608:(also known as 606:Dravet syndrome 588:Central neurons 575: 565:channelopathies 537: 533: 529: 505: 496: 464: 435: 427:window currents 243: 208:phosphorylation 196: 191: 185: 176: 148:excitable cells 144: 124:to the channel 100: 74: 59: 42:(Na) through a 28:Sodium channels 17: 12: 11: 5: 9783: 9773: 9772: 9767: 9762: 9745: 9744: 9730: 9727: 9726: 9723: 9722: 9720: 9719: 9711: 9709: 9698: 9697: 9695: 9694: 9686: 9684: 9670: 9666: 9665: 9662: 9661: 9658: 9657: 9655: 9654: 9649: 9644: 9639: 9634: 9629: 9627:Mefenamic acid 9624: 9619: 9614: 9608: 9606: 9597: 9593: 9592: 9589: 9588: 9586: 9585: 9583:Phenanthridine 9580: 9575: 9570: 9565: 9560: 9554: 9552: 9546: 9545: 9543: 9542: 9537: 9532: 9526: 9524: 9515: 9504: 9503: 9500: 9499: 9497: 9496: 9490: 9488: 9482: 9481: 9479: 9478: 9473: 9468: 9463: 9458: 9453: 9448: 9443: 9438: 9433: 9427: 9425: 9416: 9402: 9396: 9395: 9392: 9391: 9388: 9387: 9385: 9384: 9379: 9374: 9369: 9364: 9358: 9356: 9347: 9336: 9335: 9332: 9331: 9329: 9328: 9322: 9320: 9314: 9313: 9311: 9310: 9305: 9300: 9294: 9292: 9283: 9272: 9271: 9268: 9267: 9265: 9264: 9259: 9254: 9249: 9244: 9231:Atracotoxins ( 9229: 9223: 9221: 9215: 9214: 9212: 9211: 9206: 9201: 9191: 9186: 9177: 9176: 9174:Zetekitoxin AB 9171: 9166: 9161: 9156: 9147: 9146: 9141: 9136: 9131: 9126: 9121: 9116: 9111: 9106: 9101: 9092: 9091: 9086: 9081: 9076: 9074:Proxymetacaine 9071: 9066: 9061: 9056: 9051: 9046: 9041: 9036: 9031: 9026: 9021: 9016: 9011: 9006: 9001: 8996: 8991: 8986: 8984:Chloroprocaine 8981: 8976: 8971: 8957: 8952: 8947: 8942: 8930: 8929: 8924: 8919: 8914: 8909: 8904: 8899: 8894: 8889: 8884: 8879: 8874: 8869: 8864: 8859: 8854: 8849: 8844: 8839: 8834: 8829: 8824: 8819: 8814: 8809: 8804: 8799: 8790: 8789: 8784: 8779: 8774: 8769: 8764: 8759: 8754: 8749: 8744: 8739: 8734: 8729: 8724: 8719: 8714: 8709: 8704: 8695: 8694: 8685: 8683: 8674: 8660: 8654: 8653: 8650: 8649: 8646: 8645: 8643: 8642: 8636: 8634: 8628: 8627: 8625: 8624: 8619: 8614: 8609: 8603: 8601: 8592: 8581: 8580: 8577: 8576: 8574: 8573: 8568: 8563: 8558: 8553: 8548: 8539: 8533: 8531: 8525: 8524: 8522: 8521: 8516: 8507: 8501: 8499: 8490: 8482: 8476: 8475: 8472: 8471: 8469: 8468: 8451: 8450: 8445: 8440: 8435: 8430: 8425: 8420: 8415: 8410: 8405: 8400: 8395: 8390: 8385: 8372: 8365: 8363: 8357: 8356: 8354: 8353: 8348: 8343: 8338: 8333: 8328: 8323: 8318: 8313: 8296: 8295: 8290: 8285: 8280: 8275: 8270: 8265: 8260: 8258:Glyclopyramide 8255: 8250: 8245: 8240: 8235: 8230: 8225: 8220: 8215: 8213:Chlorpropamide 8210: 8205: 8192: 8185: 8183: 8174: 8163: 8162: 8159: 8158: 8156: 8155: 8150: 8140: 8134: 8132: 8126: 8125: 8123: 8122: 8117: 8112: 8102: 8096: 8095: 8090: 8085: 8080: 8075: 8070: 8065: 8060: 8055: 8050: 8045: 8040: 8035: 8030: 8025: 8020: 8015: 8010: 8005: 8000: 7995: 7990: 7985: 7980: 7975: 7970: 7965: 7960: 7958:Clarithromycin 7955: 7950: 7948:Chlorpromazine 7945: 7940: 7935: 7930: 7925: 7920: 7915: 7910: 7905: 7900: 7895: 7887: 7879: 7878: 7873: 7868: 7863: 7858: 7853: 7848: 7843: 7838: 7833: 7828: 7823: 7818: 7813: 7808: 7803: 7798: 7793: 7788: 7783: 7778: 7773: 7768: 7763: 7758: 7753: 7748: 7743: 7738: 7733: 7728: 7723: 7718: 7713: 7708: 7703: 7697: 7695: 7686: 7672: 7666: 7665: 7662: 7661: 7658: 7657: 7655: 7654: 7642: 7640: 7634: 7633: 7631: 7630: 7625: 7620: 7615: 7610: 7605: 7600: 7595: 7590: 7585: 7580: 7575: 7570: 7568:Paramethadione 7565: 7560: 7555: 7550: 7545: 7540: 7535: 7530: 7525: 7520: 7515: 7510: 7505: 7500: 7495: 7490: 7485: 7480: 7475: 7470: 7465: 7460: 7455: 7450: 7445: 7440: 7435: 7430: 7425: 7416: 7415: 7410: 7405: 7400: 7395: 7390: 7385: 7380: 7375: 7370: 7365: 7360: 7355: 7350: 7343:gabapentinoids 7336: 7330: 7329: 7324: 7319: 7314: 7309: 7304: 7299: 7294: 7289: 7284: 7279: 7274: 7269: 7264: 7259: 7254: 7249: 7244:Non-selective: 7240: 7239: 7234: 7229: 7224: 7219: 7214: 7209: 7197: 7196: 7184: 7183: 7181:ω-Agatoxin IVB 7178: 7176:ω-Agatoxin IVA 7166: 7165: 7160: 7155: 7150: 7145: 7140: 7135: 7133:Huwentoxin XVI 7130: 7125: 7120: 7108: 7107: 7102: 7097: 7092: 7087: 7085:Cyproheptadine 7082: 7077: 7072: 7067: 7055: 7050: 7045: 7040: 7035: 7030: 7025: 7020: 7015: 7010: 7005: 7000: 6995: 6980: 6975: 6970: 6965: 6950: 6945: 6940: 6935: 6930: 6925: 6920: 6915: 6910: 6905: 6900: 6895: 6890: 6885: 6880: 6875: 6870: 6865: 6860: 6855: 6850: 6845: 6843:Levniguldipine 6840: 6835: 6830: 6825: 6820: 6815: 6810: 6805: 6800: 6795: 6790: 6785: 6783:Dexniguldipine 6780: 6775: 6770: 6765: 6760: 6755: 6750: 6732: 6730: 6721: 6707: 6701: 6700: 6693: 6692: 6685: 6678: 6670: 6661: 6660: 6652: 6649: 6648: 6645: 6644: 6641: 6640: 6638: 6637: 6632: 6627: 6622: 6616: 6614: 6604: 6603: 6591: 6590: 6587: 6586: 6583: 6582: 6580: 6579: 6574: 6573: 6572: 6571: 6570: 6565: 6560: 6552: 6551: 6550: 6545: 6540: 6532: 6531: 6530: 6525: 6520: 6515: 6510: 6505: 6500: 6492: 6491: 6490: 6485: 6480: 6475: 6470: 6465: 6460: 6446: 6444: 6432: 6431: 6429: 6428: 6423: 6422: 6421: 6416: 6411: 6401: 6400: 6399: 6394: 6389: 6384: 6379: 6374: 6369: 6364: 6359: 6354: 6343: 6341: 6327: 6321: 6320: 6318: 6317: 6316: 6315: 6310: 6305: 6300: 6295: 6290: 6280: 6279: 6278: 6273: 6263: 6258: 6257: 6256: 6251: 6246: 6236: 6235: 6234: 6229: 6224: 6219: 6214: 6209: 6204: 6199: 6189: 6188: 6187: 6182: 6177: 6172: 6167: 6162: 6157: 6152: 6142: 6131: 6129: 6117: 6116: 6114: 6113: 6112: 6111: 6106: 6101: 6096: 6091: 6079: 6078: 6077: 6072: 6067: 6057: 6056: 6055: 6050: 6045: 6040: 6029: 6027: 6015: 6014: 6012: 6011: 6005: 6003: 6001:Proton channel 5991: 5990: 5988: 5987: 5986: 5985: 5980: 5970: 5969: 5968: 5963: 5958: 5953: 5948: 5943: 5938: 5928: 5927: 5926: 5921: 5916: 5911: 5906: 5901: 5896: 5891: 5886: 5876: 5871: 5870: 5869: 5868: 5867: 5862: 5857: 5852: 5842: 5841: 5840: 5835: 5825: 5824: 5823: 5807: 5805: 5789: 5788: 5776: 5775: 5772: 5771: 5768: 5767: 5765: 5764: 5759: 5758: 5757: 5752: 5747: 5737: 5732: 5727: 5726: 5725: 5720: 5715: 5710: 5700: 5699: 5698: 5693: 5688: 5678: 5673: 5672: 5671: 5670: 5665: 5660: 5653: 5652: 5651: 5646: 5641: 5634: 5633: 5632: 5627: 5620: 5619: 5618: 5613: 5608: 5601: 5600: 5599: 5594: 5587: 5586: 5585: 5580: 5575: 5570: 5565: 5555: 5550: 5549: 5548: 5547: 5542: 5537: 5532: 5525: 5524: 5523: 5516: 5515: 5514: 5509: 5504: 5497: 5496: 5495: 5490: 5485: 5480: 5473: 5472: 5471: 5466: 5459: 5458: 5457: 5452: 5447: 5442: 5437: 5432: 5427: 5422: 5412: 5407: 5405: 5399: 5398: 5396: 5395: 5394: 5393: 5388: 5383: 5378: 5373: 5368: 5363: 5358: 5353: 5348: 5343: 5338: 5333: 5328: 5323: 5312: 5310: 5304: 5303: 5301: 5300: 5299: 5298: 5293: 5288: 5283: 5278: 5273: 5264: 5260: 5259: 5258: 5253: 5248: 5243: 5234: 5226: 5225: 5224: 5219: 5214: 5209: 5204: 5199: 5190: 5186: 5182: 5177: 5175: 5169: 5168: 5166: 5165: 5164: 5163: 5158: 5153: 5148: 5143: 5138: 5133: 5128: 5119: 5115: 5114: 5113: 5105: 5104: 5103: 5098: 5093: 5083: 5082: 5081: 5076: 5071: 5066: 5061: 5050: 5048: 5038: 5037: 5022: 5021: 5018: 5017: 5014: 5013: 5011: 5010: 5009: 5008: 5003: 4998: 4993: 4983: 4979: 4978: 4977: 4972: 4967: 4962: 4957: 4952: 4947: 4942: 4937: 4932: 4922: 4917: 4915: 4909: 4908: 4906: 4905: 4904: 4903: 4898: 4893: 4888: 4877: 4875: 4868: 4867: 4865: 4864: 4863: 4862: 4857: 4852: 4847: 4836: 4834: 4826: 4825: 4822:Sodium channel 4810: 4809: 4806: 4805: 4802: 4801: 4799: 4798: 4797: 4796: 4791: 4781: 4780: 4779: 4774: 4769: 4764: 4753: 4752: 4751: 4750: 4745: 4740: 4735: 4725: 4724: 4723: 4718: 4713: 4708: 4698: 4697: 4696: 4691: 4681: 4676: 4675: 4674: 4673: 4668: 4663: 4653: 4645: 4640: 4632: 4627: 4619: 4618: 4617: 4607: 4599: 4594: 4586: 4585: 4584: 4579: 4574: 4569: 4559: 4550: 4548: 4542: 4541: 4539: 4538: 4537: 4536: 4531: 4526: 4516: 4515: 4514: 4509: 4504: 4493: 4491: 4483: 4482: 4467: 4466: 4450: 4449: 4442: 4435: 4427: 4421: 4420: 4397: 4385: 4384:External links 4382: 4380: 4379: 4350:(1): 367–377. 4330: 4273: 4238: 4189: 4158:(7): 4782–91. 4138: 4087: 4038: 4009:(6): 693–715. 3986: 3957:(6): 1065–83. 3937: 3922: 3896: 3861:(1): 192–199. 3841: 3804:(2): 245–251. 3784: 3747:(4): 721–726. 3726: 3689:(6): 965–976. 3669: 3601: 3564:(7): 624–629. 3541: 3482: 3445:(3): 488–499. 3422: 3385:(8): 873–880. 3361: 3293: 3256:(2): 371–383. 3231: 3173: 3152:(2): 287–300. 3132: 3086: 3049:(6): 899–911. 3022: 2968: 2919: 2878: 2819: 2770: 2726: 2677: 2628: 2601:(6): 397–407. 2585: 2544: 2503: 2476: 2432: 2383: 2332: 2283: 2234: 2184: 2141: 2090: 2042: 2013: 1963: 1936:(4): 397–409. 1913: 1865: 1853: 1841: 1829: 1817: 1808: 1771:Genome Biology 1757: 1742: 1716: 1709: 1688: 1667: 1636: 1634: 1631: 1629: 1628: 1622: 1613: 1607: 1601: 1595: 1588: 1586: 1583: 1578: 1574: 1570: 1566: 1562: 1558: 1554: 1550: 1546: 1542: 1538: 1534: 1531: 1525: 1522: 1512: 1509: 1503: 1500: 1494: 1491: 1481: 1478: 1472: 1469: 1458: 1439:both activate 1404: 1401: 1395: 1392: 1391: 1390: 1389: 1388: 1385:Scorpion venom 1382: 1377: 1371:-based toxins 1361: 1358: 1357: 1356: 1355: 1354: 1349: 1342: 1337: 1332: 1327: 1322: 1316:-based toxins 1300: 1297: 1292:Main article: 1289: 1286: 1284: 1281: 1226:Main article: 1223: 1220: 1193: 1190: 1187: 1186: 1183: 1180: 1176: 1172: 1168: 1165: 1158: 1153: 1148: 1147: 1142: 1139: 1135: 1131: 1127: 1124: 1117: 1112: 1107: 1106: 1101: 1098: 1094: 1090: 1086: 1082: 1079: 1072: 1067: 1062: 1061: 1055: 1052: 1048: 1044: 1041: 1034: 1029: 1024: 1023: 1017: 1014: 1013:Assembles with 1011: 1006: 949: 946: 940: 937: 934: 933: 930: 927: 920: 916: 911: 910: 907: 904: 897: 892: 887: 886: 883: 880: 873: 868: 863: 862: 844: 831: 824: 819: 814: 813: 796: 785: 778: 773: 768: 767: 737: 734: 727: 722: 717: 716: 703: 698: 691: 686: 681: 680: 677: 674: 667: 662: 657: 656: 642: 639: 632: 627: 622: 621: 594: 585: 578: 573: 568: 567: 561: 558: 555: 535: 531: 530:1.1 through Na 527: 504: 503:Alpha subunits 501: 495: 492: 463: 460: 443:Hodgkin–Huxley 434: 431: 419:deinactivation 404: 403: 400: 397: 394: 391: 387: 386: 383: 380: 377: 374: 370: 369: 366: 363: 360: 357: 353: 352: 349: 346: 343: 340: 336: 335: 332: 329: 326: 323: 319: 318: 315: 312: 309: 306: 302: 301: 298: 295: 292: 289: 285: 284: 281: 278: 275: 272: 242: 239: 216:alpha subunits 195: 192: 187:Main article: 184: 181: 175: 172: 143: 140: 137: 136: 133: 130: 126: 125: 118: 115: 109: 108: 101: 99: 98: 95: 92: 89: 85: 83: 77: 76: 71: 68: 58: 57:Classification 55: 15: 9: 6: 4: 3: 2: 9782: 9771: 9768: 9766: 9763: 9761: 9758: 9757: 9755: 9742: 9741: 9737: 9734: 9728: 9717: 9713: 9712: 9710: 9705: 9699: 9692: 9688: 9687: 9685: 9680: 9674: 9671: 9667: 9653: 9650: 9648: 9645: 9643: 9640: 9638: 9637:Niflumic acid 9635: 9633: 9630: 9628: 9625: 9623: 9620: 9618: 9615: 9613: 9610: 9609: 9607: 9605: 9601: 9598: 9594: 9584: 9581: 9579: 9576: 9574: 9571: 9569: 9566: 9564: 9561: 9559: 9556: 9555: 9553: 9551: 9547: 9541: 9538: 9536: 9533: 9531: 9530:Glibenclamide 9528: 9527: 9525: 9523: 9519: 9516: 9511: 9505: 9495: 9492: 9491: 9489: 9487: 9483: 9477: 9476:Niflumic acid 9474: 9472: 9469: 9467: 9464: 9462: 9461:Glibenclamide 9459: 9457: 9454: 9452: 9449: 9447: 9444: 9442: 9439: 9437: 9434: 9432: 9429: 9428: 9426: 9424: 9420: 9417: 9412: 9406: 9403: 9401: 9397: 9383: 9380: 9378: 9375: 9373: 9370: 9368: 9365: 9363: 9360: 9359: 9357: 9355: 9351: 9348: 9343: 9337: 9327: 9324: 9323: 9321: 9319: 9315: 9309: 9306: 9304: 9301: 9299: 9296: 9295: 9293: 9291: 9287: 9284: 9279: 9273: 9263: 9260: 9258: 9257:Grayanotoxins 9255: 9253: 9250: 9248: 9247:Batrachotoxin 9245: 9242: 9238: 9234: 9233:ω-Atracotoxin 9230: 9228: 9225: 9224: 9222: 9220: 9216: 9210: 9207: 9205: 9202: 9199: 9195: 9192: 9190: 9187: 9185: 9184:Buprenorphine 9182: 9179: 9178: 9175: 9172: 9170: 9167: 9165: 9162: 9160: 9157: 9155: 9152: 9149: 9148: 9145: 9142: 9140: 9137: 9135: 9132: 9130: 9127: 9125: 9122: 9120: 9117: 9115: 9112: 9110: 9107: 9105: 9102: 9100: 9097: 9094: 9093: 9090: 9087: 9085: 9082: 9080: 9077: 9075: 9072: 9070: 9067: 9065: 9062: 9060: 9057: 9055: 9052: 9050: 9047: 9045: 9042: 9040: 9037: 9035: 9032: 9030: 9027: 9025: 9022: 9020: 9017: 9015: 9012: 9010: 9007: 9005: 9002: 9000: 8997: 8995: 8992: 8990: 8987: 8985: 8982: 8980: 8977: 8975: 8972: 8969: 8965: 8961: 8958: 8956: 8953: 8951: 8948: 8946: 8943: 8941: 8939: 8935: 8932: 8931: 8928: 8925: 8923: 8920: 8918: 8917:Valproic acid 8915: 8913: 8910: 8908: 8905: 8903: 8900: 8898: 8895: 8893: 8890: 8888: 8885: 8883: 8880: 8878: 8875: 8873: 8870: 8868: 8865: 8863: 8862:Oxitriptyline 8860: 8858: 8857:Oxcarbazepine 8855: 8853: 8850: 8848: 8847:Licarbazepine 8845: 8843: 8840: 8838: 8835: 8833: 8830: 8828: 8825: 8823: 8820: 8818: 8815: 8813: 8810: 8808: 8805: 8803: 8802:Carbamazepine 8800: 8798: 8795: 8792: 8791: 8788: 8785: 8783: 8780: 8778: 8775: 8773: 8770: 8768: 8765: 8763: 8760: 8758: 8755: 8753: 8750: 8748: 8745: 8743: 8740: 8738: 8735: 8733: 8730: 8728: 8725: 8723: 8720: 8718: 8715: 8713: 8710: 8708: 8705: 8703: 8700: 8697: 8696: 8693: 8690: 8689:Antianginals: 8687: 8686: 8684: 8682: 8678: 8675: 8670: 8664: 8661: 8659: 8655: 8641: 8638: 8637: 8635: 8633: 8629: 8623: 8622:Norfluoxetine 8620: 8618: 8615: 8613: 8610: 8608: 8605: 8604: 8602: 8600: 8596: 8593: 8588: 8582: 8572: 8569: 8567: 8564: 8562: 8559: 8557: 8556:Niflumic acid 8554: 8552: 8549: 8547: 8544: 8542: 8535: 8534: 8532: 8530: 8526: 8520: 8517: 8515: 8512: 8510: 8503: 8502: 8500: 8498: 8494: 8491: 8486: 8477: 8467: 8464: 8459: 8453: 8452: 8449: 8446: 8444: 8441: 8439: 8436: 8434: 8431: 8429: 8426: 8424: 8421: 8419: 8416: 8414: 8411: 8409: 8408:Levcromakalim 8406: 8404: 8401: 8399: 8396: 8394: 8391: 8389: 8386: 8384: 8381: 8376: 8367: 8366: 8364: 8362: 8358: 8352: 8349: 8347: 8344: 8342: 8339: 8337: 8334: 8332: 8329: 8327: 8324: 8322: 8319: 8317: 8314: 8312: 8309: 8304: 8298: 8297: 8294: 8291: 8289: 8286: 8284: 8281: 8279: 8276: 8274: 8271: 8269: 8266: 8264: 8261: 8259: 8256: 8254: 8251: 8249: 8246: 8244: 8241: 8239: 8236: 8234: 8231: 8229: 8226: 8224: 8221: 8219: 8216: 8214: 8211: 8209: 8206: 8204: 8203:Acetohexamide 8201: 8196: 8187: 8186: 8184: 8182: 8178: 8175: 8170: 8164: 8154: 8151: 8149: 8146: 8144: 8136: 8135: 8133: 8131: 8127: 8121: 8118: 8116: 8113: 8111: 8108: 8106: 8098: 8097: 8094: 8091: 8089: 8086: 8084: 8081: 8079: 8076: 8074: 8071: 8069: 8066: 8064: 8061: 8059: 8056: 8054: 8051: 8049: 8048:Roxithromycin 8046: 8044: 8041: 8039: 8036: 8034: 8031: 8029: 8026: 8024: 8021: 8019: 8016: 8014: 8011: 8009: 8006: 8004: 8001: 7999: 7996: 7994: 7991: 7989: 7986: 7984: 7981: 7979: 7976: 7974: 7971: 7969: 7966: 7964: 7961: 7959: 7956: 7954: 7951: 7949: 7946: 7944: 7941: 7939: 7936: 7934: 7931: 7929: 7926: 7924: 7921: 7919: 7916: 7914: 7911: 7909: 7906: 7904: 7901: 7899: 7896: 7894: 7891: 7885: 7881: 7880: 7877: 7874: 7872: 7869: 7867: 7864: 7862: 7859: 7857: 7854: 7852: 7849: 7847: 7844: 7842: 7839: 7837: 7834: 7832: 7829: 7827: 7824: 7822: 7819: 7817: 7814: 7812: 7809: 7807: 7804: 7802: 7799: 7797: 7794: 7792: 7789: 7787: 7784: 7782: 7779: 7777: 7774: 7772: 7769: 7767: 7764: 7762: 7759: 7757: 7754: 7752: 7749: 7747: 7744: 7742: 7741:Charybdotoxin 7739: 7737: 7734: 7732: 7729: 7727: 7724: 7722: 7719: 7717: 7714: 7712: 7709: 7707: 7704: 7702: 7699: 7698: 7696: 7694: 7690: 7687: 7682: 7676: 7673: 7671: 7667: 7653: 7650: 7648: 7644: 7643: 7641: 7639: 7635: 7629: 7626: 7624: 7623:Trimethadione 7621: 7619: 7616: 7614: 7611: 7609: 7606: 7604: 7601: 7599: 7596: 7594: 7591: 7589: 7586: 7584: 7581: 7579: 7576: 7574: 7571: 7569: 7566: 7564: 7561: 7559: 7556: 7554: 7551: 7549: 7546: 7544: 7541: 7539: 7536: 7534: 7531: 7529: 7526: 7524: 7521: 7519: 7516: 7514: 7511: 7509: 7506: 7504: 7501: 7499: 7496: 7494: 7491: 7489: 7486: 7484: 7481: 7479: 7476: 7474: 7471: 7469: 7466: 7464: 7463:Diproteverine 7461: 7459: 7456: 7454: 7451: 7449: 7446: 7444: 7441: 7439: 7436: 7434: 7431: 7429: 7426: 7424: 7421: 7418: 7417: 7414: 7411: 7409: 7406: 7404: 7401: 7399: 7396: 7394: 7391: 7389: 7386: 7384: 7381: 7379: 7376: 7374: 7371: 7369: 7366: 7364: 7361: 7359: 7356: 7354: 7351: 7349: 7346: 7344: 7340: 7332: 7331: 7328: 7325: 7323: 7322:Ruthenium red 7320: 7318: 7315: 7313: 7310: 7308: 7305: 7303: 7300: 7298: 7297:Levetiracetam 7295: 7293: 7290: 7288: 7285: 7283: 7280: 7278: 7275: 7273: 7270: 7268: 7265: 7263: 7260: 7258: 7255: 7253: 7250: 7248: 7247:ω-Agatoxin TK 7245: 7242: 7241: 7238: 7235: 7233: 7230: 7228: 7225: 7223: 7220: 7218: 7217:Niflumic acid 7215: 7213: 7210: 7208: 7205: 7203: 7199: 7198: 7195: 7192: 7190: 7186: 7185: 7182: 7179: 7177: 7174: 7172: 7168: 7167: 7164: 7161: 7159: 7156: 7154: 7151: 7149: 7146: 7144: 7141: 7139: 7136: 7134: 7131: 7129: 7126: 7124: 7121: 7119: 7116: 7114: 7110: 7109: 7106: 7103: 7101: 7098: 7096: 7093: 7091: 7088: 7086: 7083: 7081: 7078: 7076: 7073: 7071: 7068: 7066: 7063: 7059: 7056: 7054: 7051: 7049: 7046: 7044: 7041: 7039: 7036: 7034: 7031: 7029: 7026: 7024: 7021: 7019: 7016: 7014: 7011: 7009: 7006: 7004: 7001: 6999: 6996: 6994: 6991: 6989: 6984: 6981: 6979: 6976: 6974: 6971: 6969: 6966: 6964: 6961: 6959: 6954: 6951: 6949: 6946: 6944: 6941: 6939: 6936: 6934: 6931: 6929: 6926: 6924: 6921: 6919: 6916: 6914: 6911: 6909: 6906: 6904: 6901: 6899: 6896: 6894: 6891: 6889: 6886: 6884: 6881: 6879: 6876: 6874: 6871: 6869: 6866: 6864: 6861: 6859: 6856: 6854: 6851: 6849: 6846: 6844: 6841: 6839: 6838:Levamlodipine 6836: 6834: 6833:Lercanidipine 6831: 6829: 6826: 6824: 6821: 6819: 6816: 6814: 6811: 6809: 6806: 6804: 6801: 6799: 6796: 6794: 6791: 6789: 6786: 6784: 6781: 6779: 6776: 6774: 6771: 6769: 6766: 6764: 6761: 6759: 6756: 6754: 6751: 6749: 6746: 6744: 6740: 6738: 6734: 6733: 6731: 6729: 6725: 6722: 6717: 6711: 6708: 6706: 6702: 6698: 6691: 6686: 6684: 6679: 6677: 6672: 6671: 6668: 6658: 6657: 6650: 6636: 6633: 6631: 6630:Voltage-gated 6628: 6626: 6623: 6621: 6618: 6617: 6615: 6613: 6609: 6605: 6601: 6596: 6592: 6578: 6575: 6569: 6566: 6564: 6561: 6559: 6556: 6555: 6553: 6549: 6546: 6544: 6541: 6539: 6536: 6535: 6533: 6529: 6526: 6524: 6521: 6519: 6516: 6514: 6511: 6509: 6506: 6504: 6501: 6499: 6496: 6495: 6493: 6489: 6486: 6484: 6481: 6479: 6476: 6474: 6471: 6469: 6466: 6464: 6461: 6459: 6456: 6455: 6453: 6452: 6451: 6448: 6447: 6445: 6443: 6440: 6438: 6433: 6427: 6424: 6420: 6417: 6415: 6412: 6410: 6407: 6406: 6405: 6402: 6398: 6395: 6393: 6390: 6388: 6385: 6383: 6380: 6378: 6375: 6373: 6370: 6368: 6365: 6363: 6360: 6358: 6355: 6353: 6350: 6349: 6348: 6345: 6344: 6342: 6340: 6337: 6335: 6331: 6322: 6314: 6311: 6309: 6306: 6304: 6301: 6299: 6296: 6294: 6291: 6289: 6286: 6285: 6284: 6281: 6277: 6274: 6272: 6269: 6268: 6267: 6264: 6262: 6259: 6255: 6252: 6250: 6247: 6245: 6242: 6241: 6240: 6237: 6233: 6230: 6228: 6225: 6223: 6220: 6218: 6215: 6213: 6210: 6208: 6205: 6203: 6200: 6198: 6195: 6194: 6193: 6190: 6186: 6183: 6181: 6178: 6176: 6173: 6171: 6168: 6166: 6163: 6161: 6158: 6156: 6153: 6151: 6148: 6147: 6146: 6143: 6140: 6136: 6133: 6132: 6130: 6128: 6125: 6123: 6118: 6110: 6107: 6105: 6102: 6100: 6097: 6095: 6092: 6090: 6087: 6086: 6085: 6084: 6080: 6076: 6073: 6071: 6068: 6066: 6063: 6062: 6061: 6058: 6054: 6051: 6049: 6046: 6044: 6041: 6039: 6036: 6035: 6034: 6031: 6030: 6028: 6026: 6023: 6021: 6016: 6010: 6007: 6006: 6004: 6002: 5999: 5997: 5992: 5984: 5981: 5979: 5976: 5975: 5974: 5971: 5967: 5964: 5962: 5959: 5957: 5954: 5952: 5949: 5947: 5944: 5942: 5939: 5937: 5934: 5933: 5932: 5929: 5925: 5922: 5920: 5917: 5915: 5912: 5910: 5907: 5905: 5902: 5900: 5897: 5895: 5892: 5890: 5887: 5885: 5882: 5881: 5880: 5877: 5875: 5872: 5866: 5863: 5861: 5858: 5856: 5853: 5851: 5848: 5847: 5846: 5843: 5839: 5836: 5834: 5831: 5830: 5829: 5826: 5822: 5819: 5818: 5817: 5814: 5813: 5812: 5809: 5808: 5806: 5804: 5801: 5799: 5794: 5790: 5786: 5785:Miscellaneous 5781: 5777: 5763: 5762:Shaker (gene) 5760: 5756: 5753: 5751: 5748: 5746: 5743: 5742: 5741: 5738: 5736: 5735:minK/ISK-like 5733: 5731: 5728: 5724: 5721: 5719: 5716: 5714: 5711: 5709: 5706: 5705: 5704: 5701: 5697: 5694: 5692: 5689: 5687: 5684: 5683: 5682: 5675: 5674: 5669: 5666: 5664: 5661: 5659: 5656: 5655: 5654: 5650: 5647: 5645: 5642: 5640: 5637: 5636: 5635: 5631: 5628: 5626: 5623: 5622: 5621: 5617: 5614: 5612: 5609: 5607: 5604: 5603: 5602: 5598: 5595: 5593: 5590: 5589: 5588: 5584: 5581: 5579: 5576: 5574: 5571: 5569: 5566: 5564: 5561: 5560: 5559: 5552: 5551: 5546: 5543: 5541: 5538: 5536: 5533: 5531: 5528: 5527: 5526: 5522: 5519: 5518: 5517: 5513: 5510: 5508: 5505: 5503: 5500: 5499: 5498: 5494: 5491: 5489: 5486: 5484: 5481: 5479: 5476: 5475: 5474: 5470: 5467: 5465: 5462: 5461: 5460: 5456: 5453: 5451: 5448: 5446: 5443: 5441: 5438: 5436: 5433: 5431: 5428: 5426: 5423: 5421: 5418: 5417: 5416: 5409: 5408: 5406: 5404: 5403:Voltage-gated 5400: 5392: 5389: 5387: 5384: 5382: 5379: 5377: 5374: 5372: 5369: 5367: 5364: 5362: 5359: 5357: 5354: 5352: 5349: 5347: 5344: 5342: 5339: 5337: 5334: 5332: 5329: 5327: 5324: 5322: 5319: 5318: 5317: 5314: 5313: 5311: 5309: 5305: 5297: 5294: 5292: 5289: 5287: 5284: 5282: 5279: 5277: 5274: 5272: 5269: 5268: 5267: 5261: 5257: 5254: 5252: 5249: 5247: 5244: 5242: 5239: 5238: 5237: 5230: 5227: 5223: 5220: 5218: 5215: 5213: 5210: 5208: 5205: 5203: 5200: 5198: 5195: 5194: 5193: 5187: 5185: 5179: 5178: 5176: 5174: 5170: 5162: 5159: 5157: 5154: 5152: 5149: 5147: 5144: 5142: 5139: 5137: 5134: 5132: 5129: 5127: 5124: 5123: 5122: 5116: 5112: 5109: 5108: 5106: 5102: 5099: 5097: 5094: 5092: 5089: 5088: 5087: 5084: 5080: 5077: 5075: 5072: 5070: 5067: 5065: 5062: 5060: 5057: 5056: 5055: 5052: 5051: 5049: 5047: 5043: 5039: 5035: 5032: 5027: 5023: 5007: 5004: 5002: 4999: 4997: 4994: 4992: 4989: 4988: 4987: 4980: 4976: 4973: 4971: 4968: 4966: 4963: 4961: 4958: 4956: 4953: 4951: 4948: 4946: 4943: 4941: 4938: 4936: 4933: 4931: 4928: 4927: 4926: 4919: 4918: 4916: 4914: 4913:Voltage-gated 4910: 4902: 4899: 4897: 4894: 4892: 4889: 4887: 4884: 4883: 4882: 4879: 4878: 4876: 4873: 4869: 4861: 4858: 4856: 4853: 4851: 4848: 4846: 4843: 4842: 4841: 4838: 4837: 4835: 4831: 4827: 4823: 4820: 4815: 4811: 4795: 4792: 4790: 4787: 4786: 4785: 4782: 4778: 4775: 4773: 4770: 4768: 4765: 4763: 4760: 4759: 4758: 4755: 4754: 4749: 4746: 4744: 4741: 4739: 4736: 4734: 4731: 4730: 4729: 4726: 4722: 4719: 4717: 4714: 4712: 4709: 4707: 4704: 4703: 4702: 4699: 4695: 4692: 4690: 4687: 4686: 4685: 4678: 4677: 4672: 4669: 4667: 4664: 4662: 4659: 4658: 4657: 4649: 4646: 4644: 4636: 4633: 4631: 4623: 4620: 4616: 4613: 4612: 4611: 4603: 4600: 4598: 4590: 4587: 4583: 4580: 4578: 4575: 4573: 4570: 4568: 4565: 4564: 4563: 4555: 4552: 4551: 4549: 4547: 4546:Voltage-gated 4543: 4535: 4532: 4530: 4527: 4525: 4522: 4521: 4520: 4517: 4513: 4510: 4508: 4505: 4503: 4500: 4499: 4498: 4495: 4494: 4492: 4488: 4484: 4480: 4477: 4472: 4468: 4463: 4459: 4455: 4448: 4443: 4441: 4436: 4434: 4429: 4428: 4425: 4411:on 2021-12-09 4410: 4406: 4402: 4398: 4395: 4391: 4388: 4387: 4375: 4371: 4366: 4361: 4357: 4353: 4349: 4345: 4341: 4334: 4326: 4322: 4317: 4312: 4308: 4304: 4300: 4296: 4292: 4288: 4284: 4277: 4269: 4265: 4261: 4257: 4253: 4249: 4242: 4234: 4230: 4225: 4220: 4216: 4212: 4208: 4204: 4200: 4193: 4185: 4181: 4176: 4171: 4166: 4161: 4157: 4153: 4149: 4142: 4134: 4130: 4125: 4120: 4115: 4110: 4106: 4102: 4098: 4091: 4083: 4079: 4074: 4069: 4065: 4061: 4057: 4053: 4049: 4042: 4034: 4030: 4025: 4020: 4016: 4012: 4008: 4004: 4000: 3993: 3991: 3982: 3978: 3973: 3968: 3964: 3960: 3956: 3952: 3948: 3941: 3933: 3929: 3925: 3919: 3915: 3911: 3907: 3900: 3892: 3888: 3884: 3880: 3876: 3872: 3868: 3864: 3860: 3856: 3852: 3845: 3837: 3833: 3828: 3823: 3819: 3815: 3811: 3807: 3803: 3799: 3795: 3788: 3780: 3776: 3771: 3766: 3762: 3758: 3754: 3750: 3746: 3742: 3738: 3730: 3722: 3718: 3714: 3710: 3706: 3702: 3697: 3692: 3688: 3684: 3680: 3673: 3665: 3661: 3656: 3651: 3647: 3643: 3639: 3635: 3631: 3627: 3623: 3619: 3615: 3608: 3606: 3597: 3593: 3589: 3585: 3581: 3577: 3572: 3567: 3563: 3559: 3555: 3548: 3546: 3537: 3533: 3528: 3523: 3519: 3515: 3510: 3505: 3501: 3497: 3493: 3486: 3478: 3474: 3469: 3464: 3460: 3456: 3452: 3448: 3444: 3440: 3436: 3429: 3427: 3418: 3414: 3409: 3404: 3400: 3396: 3392: 3388: 3384: 3380: 3376: 3368: 3366: 3357: 3353: 3348: 3343: 3339: 3335: 3331: 3327: 3323: 3319: 3315: 3311: 3307: 3300: 3298: 3289: 3285: 3281: 3277: 3273: 3269: 3264: 3259: 3255: 3251: 3247: 3240: 3238: 3236: 3227: 3223: 3219: 3215: 3211: 3207: 3203: 3199: 3195: 3191: 3187: 3180: 3178: 3169: 3165: 3160: 3155: 3151: 3147: 3143: 3136: 3128: 3124: 3119: 3114: 3110: 3106: 3102: 3098: 3090: 3082: 3078: 3073: 3068: 3064: 3060: 3056: 3052: 3048: 3044: 3040: 3033: 3031: 3029: 3027: 3018: 3014: 3009: 3004: 3000: 2996: 2992: 2988: 2984: 2977: 2975: 2973: 2964: 2960: 2955: 2950: 2946: 2942: 2939:(2): 427–34. 2938: 2934: 2930: 2923: 2915: 2911: 2906: 2901: 2897: 2893: 2889: 2882: 2874: 2870: 2865: 2860: 2855: 2850: 2846: 2842: 2838: 2834: 2830: 2823: 2815: 2811: 2806: 2801: 2797: 2793: 2789: 2785: 2781: 2774: 2766: 2762: 2758: 2754: 2750: 2746: 2742: 2738: 2730: 2722: 2718: 2713: 2708: 2704: 2700: 2696: 2692: 2688: 2681: 2673: 2669: 2664: 2659: 2655: 2651: 2647: 2643: 2639: 2632: 2624: 2620: 2616: 2612: 2608: 2604: 2600: 2596: 2589: 2581: 2577: 2572: 2567: 2563: 2559: 2555: 2548: 2540: 2536: 2531: 2526: 2522: 2518: 2514: 2507: 2493: 2486: 2480: 2472: 2468: 2464: 2460: 2456: 2452: 2448: 2444: 2436: 2428: 2424: 2420: 2416: 2411: 2406: 2402: 2398: 2394: 2387: 2379: 2375: 2370: 2365: 2360: 2355: 2351: 2347: 2343: 2336: 2328: 2324: 2319: 2314: 2310: 2306: 2303:(8): 2010–7. 2302: 2298: 2294: 2287: 2279: 2275: 2270: 2265: 2261: 2257: 2253: 2249: 2245: 2238: 2230: 2226: 2221: 2216: 2212: 2208: 2204: 2200: 2196: 2188: 2180: 2176: 2172: 2168: 2164: 2160: 2156: 2152: 2145: 2137: 2133: 2128: 2123: 2118: 2113: 2109: 2105: 2101: 2094: 2086: 2082: 2077: 2072: 2068: 2064: 2060: 2053: 2051: 2049: 2047: 2039: 2028: 2024: 2017: 2009: 2005: 2000: 1995: 1991: 1987: 1983: 1979: 1975: 1967: 1959: 1955: 1951: 1947: 1943: 1939: 1935: 1931: 1927: 1920: 1918: 1909: 1905: 1901: 1897: 1893: 1889: 1885: 1881: 1874: 1872: 1870: 1863: 1857: 1851: 1845: 1839: 1833: 1827: 1821: 1812: 1804: 1800: 1795: 1790: 1785: 1780: 1776: 1772: 1768: 1761: 1753: 1749: 1745: 1739: 1735: 1731: 1727: 1720: 1712: 1706: 1702: 1698: 1697:Bertil Hillel 1692: 1684: 1678: 1670: 1664: 1660: 1655: 1654: 1648: 1641: 1637: 1626: 1623: 1617: 1614: 1611: 1608: 1605: 1602: 1599: 1596: 1593: 1590: 1589: 1582: 1530: 1521: 1519: 1508: 1502:pH modulation 1499: 1490: 1487: 1477: 1468: 1466: 1462: 1454: 1453:Acetylcholine 1450: 1446: 1442: 1438: 1434: 1430: 1426: 1417: 1413: 1411: 1400: 1386: 1383: 1381: 1380:δ-Atracotoxin 1378: 1376: 1373: 1372: 1370: 1367: 1366: 1365: 1353: 1350: 1347: 1346:grayanotoxins 1343: 1341: 1338: 1336: 1333: 1331: 1328: 1326: 1325:batrachotoxin 1323: 1321: 1318: 1317: 1315: 1312: 1311: 1310: 1306: 1295: 1280: 1276: 1274: 1270: 1265: 1263: 1259: 1255: 1251: 1247: 1243: 1239: 1235: 1229: 1219: 1217: 1216:acetylcholine 1213: 1209: 1204: 1202: 1198: 1184: 1181: 1166: 1164: 1163: 1159: 1157: 1150: 1149: 1146: 1143: 1140: 1125: 1123: 1122: 1118: 1116: 1109: 1108: 1105: 1102: 1099: 1080: 1078: 1077: 1073: 1071: 1064: 1063: 1060: 1056: 1053: 1042: 1040: 1039: 1035: 1033: 1026: 1025: 1022: 1018: 1015: 1012: 1010: 1007: 1005: 1002: 1001: 997: 992: 990: 986: 982: 978: 974: 970: 966: 962: 958: 955: 954:intracellular 945: 939:Beta subunits 931: 928: 926: 925: 921: 919: 913: 912: 908: 905: 903: 902: 898: 896: 889: 888: 884: 881: 879: 878: 874: 872: 865: 864: 860: 856: 852: 848: 845: 843: 839: 838:Schwann cells 835: 832: 830: 829: 825: 823: 816: 815: 812: 808: 804: 800: 797: 794: 790: 786: 784: 783: 779: 777: 770: 769: 766: 764: 758: 754: 750: 746: 742: 738: 735: 733: 732: 728: 726: 719: 718: 715: 711: 707: 704: 702: 699: 697: 696: 692: 690: 683: 682: 678: 675: 673: 672: 668: 666: 659: 658: 655: 651: 647: 643: 640: 638: 637: 633: 631: 624: 623: 619: 615: 611: 607: 603: 599: 595: 593: 589: 586: 584: 583: 579: 577: 570: 569: 566: 562: 559: 556: 553: 552: 548: 543: 539: 524: 522: 513: 509: 500: 491: 489: 488:glutamic acid 485: 481: 477: 473: 469: 459: 456: 452: 448: 444: 440: 430: 428: 422: 420: 415: 413: 412: 401: 398: 395: 392: 389: 388: 384: 381: 378: 375: 372: 371: 367: 364: 361: 358: 355: 354: 350: 347: 344: 341: 338: 337: 333: 330: 327: 324: 321: 320: 316: 313: 310: 307: 304: 303: 299: 296: 293: 290: 287: 286: 282: 279: 276: 273: 270: 269: 266: 264: 260: 256: 252: 247: 238: 234: 232: 228: 223: 221: 220:beta subunits 217: 209: 205: 204:glycosylation 200: 190: 180: 171: 169: 165: 161: 157: 153: 149: 134: 131: 128: 127: 123: 119: 116: 114: 111: 110: 106: 102: 97:"Nav channel" 96: 93: 90: 87: 86: 84: 82: 79: 78: 72: 69: 66: 65: 62: 54: 52: 48: 45: 41: 38:, conducting 37: 33: 29: 21: 9732: 9731: 9642:Talniflumate 9180: 9169:Tetrodotoxin 9159:Neosaxitoxin 9150: 9095: 9069:Propoxycaine 9004:Dimethocaine 8937: 8933: 8902:Valnoctamide 8832:Fosphenytoin 8793: 8767:Procainamide 8757:Pilsicainide 8712:Disopyramide 8698: 8688: 8657: 8536: 8504: 8454: 8368: 8336:Ethosuximide 8321:Cloperastine 8299: 8268:Metahexamide 8263:Glycyclamide 8223:Glibornuride 8188: 8137: 8099: 8078:Thioridazine 8033:Promethazine 8018:Orphenadrine 8008:Ketoconazole 7993:Erythromycin 7882: 7645: 7573:Phensuximide 7553:Ochratoxin A 7493:Ethosuximide 7419: 7341:-selective ( 7333: 7243: 7200: 7187: 7169: 7118:ω-Conotoxins 7111: 7061: 7043:Norverapamil 7008:Dexverapamil 6986: 6960:derivatives: 6956: 6953:Vatanidipine 6948:Trombodipine 6913:Palonidipine 6898:Nitrendipine 6853:Mepirodipine 6758:Azelnidipine 6741: 6735: 6653: 6620:Ligand-gated 6611: 6599: 6442:Gap junction 6435: 6324: 6120: 6081: 6059: 6032: 6018: 5994: 5972: 5930: 5878: 5844: 5827: 5815: 5796: 5784: 5739: 5702: 5676: 5553: 5410: 5315: 5262: 5232: 5188: 5117: 5030: 4981: 4920: 4821: 4818: 4727: 4700: 4679: 4651: 4638: 4625: 4605: 4592: 4557: 4490:Ligand-gated 4475: 4458:ion channels 4413:. Retrieved 4409:the original 4404: 4347: 4343: 4333: 4290: 4286: 4276: 4254:(3): 304–8. 4251: 4247: 4241: 4206: 4202: 4192: 4155: 4151: 4141: 4104: 4100: 4090: 4055: 4051: 4041: 4006: 4002: 3954: 3950: 3940: 3905: 3899: 3858: 3854: 3844: 3801: 3797: 3787: 3744: 3740: 3729: 3686: 3682: 3672: 3621: 3617: 3561: 3557: 3499: 3496:PLOS Biology 3495: 3485: 3442: 3438: 3382: 3379:EMBO Reports 3378: 3313: 3309: 3253: 3249: 3193: 3190:FEBS Letters 3189: 3149: 3145: 3135: 3100: 3096: 3089: 3046: 3042: 2990: 2986: 2936: 2932: 2922: 2895: 2891: 2881: 2836: 2832: 2822: 2787: 2783: 2773: 2740: 2736: 2729: 2694: 2690: 2680: 2645: 2641: 2631: 2598: 2594: 2588: 2561: 2557: 2547: 2520: 2516: 2506: 2495:. Retrieved 2491: 2479: 2446: 2442: 2435: 2403:(1): 13–25. 2400: 2396: 2386: 2349: 2345: 2335: 2300: 2296: 2286: 2251: 2247: 2237: 2202: 2198: 2187: 2154: 2150: 2144: 2107: 2103: 2093: 2066: 2062: 2037: 2031:. Retrieved 2016: 1981: 1977: 1966: 1933: 1929: 1886:(1): 42–54. 1883: 1879: 1856: 1844: 1832: 1820: 1811: 1774: 1770: 1760: 1725: 1719: 1700: 1691: 1652: 1645:Jessell TM, 1640: 1536: 1527: 1514: 1505: 1496: 1483: 1474: 1425:tetrodotoxin 1422: 1406: 1397: 1363: 1308: 1277: 1266: 1249: 1246:depolarizing 1231: 1205: 1197:Ligand-gated 1195: 1160: 1119: 1074: 1036: 1008: 1004:Protein name 1003: 995: 957:cytoskeleton 951: 942: 922: 899: 875: 859:fibromyalgia 826: 780: 760: 729: 693: 669: 634: 617: 613: 609: 580: 554:Protein name 546: 540: 525: 517: 511: 497: 465: 436: 426: 423: 418: 416: 409: 407: 368:Repolarized 334:Depolarized 262: 258: 254: 248: 244: 235: 224: 213: 177: 164:rising phase 145: 60: 36:ion channels 27: 26: 9308:Triamterene 9262:Poneratoxin 9252:Ciguatoxins 9139:Raxatrigine 9134:Ralfinamide 9129:PF-05089771 9124:PF-04531083 9096:Analgesics: 9054:Piperocaine 9039:Meprylcaine 9034:Mepivacaine 8989:Cinchocaine 8968:Ropivacaine 8960:Bupivacaine 8887:Sipatrigine 8872:Pheneturide 8867:Phenacemide 8852:Mephenytoin 8837:Lamotrigine 8817:Elpetrigine 8772:Propafenone 8717:Dronedarone 8293:Tolbutamide 8283:Repaglinide 8278:Nateglinide 8273:Mitiglinide 8253:Glisoxepide 8238:Glimepiride 8228:Glicaramide 8208:Carbutamide 8110:Linopirdine 8093:Vernakalant 8083:Tolterodine 8073:Terfenadine 8063:Tamulotoxin 8058:Solifenacin 8028:PNU-282,987 8003:Haloperidol 7998:Gigactonine 7978:Domperidone 7963:Darifenacin 7928:Bedaquiline 7913:Azaspiracid 7876:Vernakalant 7811:Linopirdine 7771:Dronedarone 7761:Dendrotoxin 7746:Clamikalant 7618:Tolperisone 7613:Tetrandrine 7603:Sipatrigine 7598:Silperisone 7583:Prenylamine 7523:Lidoflazine 7478:Elpetrigine 7388:Mirogabalin 7292:Lamotrigine 7287:Flunarizine 7282:Efonidipine 7272:Cinnarizine 7267:Cilnidipine 7222:NNC 55-0396 7148:Ralfinamide 7095:Fantofarone 7090:Dronedarone 7075:Budiodarone 7070:Brinazarone 7033:Levemopamil 6933:Sornidipine 6928:Sagandipine 6918:Pranidipine 6893:Nisoldipine 6883:Nilvadipine 6873:Niguldipine 6863:Nicardipine 6828:Lemildipine 6813:Iganidipine 6808:Furnidipine 6773:Cronidipine 6768:Clevidipine 6763:Barnidipine 6753:Aranidipine 6625:Light-gated 5107:IK channel 4293:(1): 6304. 3624:(1): 5831. 2993:(1): 7–57. 1984:(1): 1416. 1610:Ion channel 1437:neurotensin 1433:Substance P 1375:μ-Conotoxin 1352:veratridine 1185:none known 973:Fibronectin 932:none known 751:, familial 399:Deactivated 365:Inactivated 348:Inactivated 174:Selectivity 40:sodium ions 9754:Categories 9612:Bumetanide 9550:Activators 9540:Piretanide 9535:Lonidamine 9486:Activators 9471:Mibefradil 9466:Mefloquine 9456:Furosemide 9451:Fluoxetine 9431:Crofelemer 9318:Activators 9241:Versutoxin 9237:Robustoxin 9219:Activators 9204:Safinamide 9154:Conotoxins 9089:Trimecaine 9084:Tetracaine 9059:Prilocaine 9049:Orthocaine 9024:Iontocaine 9019:Hexylcaine 9014:Etidocaine 8955:Benzocaine 8945:Amylocaine 8927:Zonisamide 8922:Valpromide 8892:Topiramate 8882:Rufinamide 8842:Lacosamide 8807:Cenobamate 8762:Prajmaline 8752:Moricizine 8747:Mexiletine 8742:Lorcainide 8727:Flecainide 8692:Ranolazine 8632:Activators 8617:Fluoxetine 8561:Nimesulide 8543:-specific: 8529:Activators 8511:-specific: 8463:-specific: 8443:Rilmakalim 8433:Nicorandil 8393:Cromakalim 8380:-specific: 8361:Activators 8351:Tipepidine 8341:Ifenprodil 8316:Caramiphen 8308:-specific: 8288:Tolazamide 8248:Gliquidone 8233:Gliclazide 8200:-specific: 8153:Retigabine 8148:Flupirtine 8145:-specific: 8130:Activators 8107:-specific: 8088:Vanoxerine 8068:Terodiline 8053:Sertindole 8043:Ranolazine 7908:Astemizole 7898:Amiodarone 7866:Terikalant 7841:Pinokalant 7826:Nifekalant 7821:Maurotoxin 7816:Lolitrem B 7806:Kaliotoxin 7766:Dofetilide 7756:Dalazatide 7751:Conotoxins 7721:Amiodarone 7716:Almokalant 7638:Activators 7628:Valperinol 7608:Terodiline 7548:Naftopidil 7538:Mesuximide 7468:Enpiperate 7448:Cycleanine 7433:Bevantolol 7423:Bencyclane 7413:Pregabalin 7403:PD-299,685 7398:PD-217,014 7393:PD-200,347 7383:Imagabalin 7373:Gabapentin 7363:Atagabalin 7353:Arbaclofen 7312:Mibefradil 7307:Loperamide 7302:Lomerizine 7277:Dotarizine 7257:Benidipine 7237:Zonisamide 7153:Safinamide 7128:Caroverine 7080:Celivarone 7028:Gallopamil 6983:Siratiazem 6973:Iprotiazem 6963:Clentiazem 6943:Tiamdipine 6938:Teludipine 6903:Olradipine 6888:Nimodipine 6878:Niludipine 6868:Nifedipine 6858:Mesudipine 6848:Manidipine 6823:Lacidipine 6818:Isradipine 6803:Flordipine 6798:Felodipine 6793:Elnadipine 6788:Elgodipine 6778:Darodipine 6748:Amlodipine 5828:Bestrophin 5086:SK channel 5054:BK channel 4728:γ-subunits 4701:β-subunits 4684:δ-subunits 4415:2008-12-18 3502:(3): e55. 3118:10453/5728 2497:2020-07-16 2033:2009-10-30 2021:Lossin C. 1777:(3): 207. 1633:References 1553:1.3 and Na 1449:G-proteins 1340:delphinine 1335:ciguatoxin 1330:brevetoxin 1303:See also: 1299:Activators 1269:K channels 1244:, further 989:ectodomain 644:inherited 472:amino acid 455:population 390:Rebounding 300:Polarized 103:change in 34:that form 9733:See also: 9632:Mepacrine 9578:Ivacaftor 9494:Carbachol 9377:Ibuprofen 9367:Amiloride 9326:Solnatide 9298:Amiloride 9227:Aconitine 9189:Evenamide 9164:Saxitoxin 9079:Risocaine 9029:Lidocaine 8974:Butacaine 8950:Articaine 8877:Phenytoin 8787:Tocainide 8782:Sparteine 8777:Quinidine 8737:Lorajmine 8732:Lidocaine 8722:Encainide 8707:Aprindine 8448:Sarakalim 8438:Pinacidil 8428:Naminidil 8418:Minoxidil 8413:Mazokalim 8398:Diazoxide 8388:Bimakalim 8383:Aprikalim 8346:Tertiapin 8326:Clozapine 8243:Glipizide 8038:Quinidine 7988:Ergtoxins 7953:Cisapride 7943:BRL-32872 7923:Azimilide 7886:(KCNH2, K 7861:Tedisamil 7846:Quinidine 7836:Paxilline 7801:Inakalant 7796:Ibutilide 7781:Hanatoxin 7736:Bunaftine 7731:Bretylium 7726:Azimilide 7711:Adekalant 7670:Potassium 7652:Bay K8644 7593:Sesamodil 7543:Monatepil 7533:Manoalide 7528:Magnesium 7513:Imepitoin 7503:Fendiline 7483:Ethadione 7473:Eperisone 7453:Dauricine 7428:Berbamine 7339:δ subunit 7143:PD-173212 7058:Verapamil 7048:Ronipamil 7038:Nexopamil 7023:Falipamil 7018:Etripamil 7003:Devapamil 6998:Dagapamil 6978:Nictiazem 6968:Diltiazem 6958:Diltiazem 6908:Oxodipine 6656:disorders 6654:see also 6437:Cytoplasm 6347:Aquaporin 5816:Anoctamin 5639:11.1/hERG 3875:0920-9964 3818:1531-8257 3761:1537-6605 3705:0896-6273 3646:2041-1723 3580:0960-9822 3518:1545-7885 3459:1097-4199 3399:1469-3178 3338:1476-4687 3272:0092-8674 3210:0014-5793 3063:1097-4199 2254:: 17–25. 1677:cite book 1647:Kandel ER 1598:Chronaxie 1429:verapamil 1320:aconitine 1250:excitable 1130:1.1 to Na 1093:1.5 to Na 1047:1.1 to Na 1009:Gene link 739:Cardiac: 512:Figure 1. 494:Diversity 439:Markovian 373:Undershot 314:Activated 227:conserved 194:Structure 9718:instead. 9693:instead. 9604:Blockers 9596:Unsorted 9522:Blockers 9423:Blockers 9400:Chloride 9362:A-317567 9354:Blockers 9303:Benzamil 9290:Blockers 9119:NKTR-171 9114:GDC-0276 9109:Funapide 9104:DSP-2230 9099:AZD-3161 9064:Procaine 8979:Butamben 8827:Ethotoin 8702:Ajmaline 8681:Blockers 8640:Riluzole 8599:Blockers 8497:Blockers 8403:Emakalim 8181:Blockers 8023:Pimozide 7893:Ajmaline 7693:Blockers 7508:Fostedil 7438:Canadine 7408:Phenibut 7368:Baclofen 7317:NP078585 7262:Bepridil 7100:SR-33805 7053:Tiapamil 7013:Emopamil 6993:Anipamil 6728:Blockers 6450:Connexin 5730:minK/ISK 4374:30362397 4344:Channels 4325:29674667 4233:16873405 4184:23283979 4133:22701426 4082:12181282 3932:29460150 3891:21402201 3883:20889312 3836:24227479 3779:24075186 3721:14910947 3713:16364900 3664:33203861 3588:17350263 3536:18336069 3477:21040849 3417:19575010 3356:19092807 3288:17165089 3280:17448995 3226:26183219 3218:10094463 3168:10491073 3127:11171353 3081:22196327 3017:26671757 2963:11470829 2914:15833746 2814:11567041 2765:21411801 2757:16817858 2721:15282281 2672:15317864 2623:22885909 2615:11389473 2580:11997395 2539:10753953 2427:17928749 2419:10798388 2378:22348792 2327:16075041 2278:27875746 2229:24613995 2179:44433455 2171:22875823 2136:30146301 2085:30672368 2027:Archived 2008:35301303 1950:16382098 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