655:(i.e. the membrane potential at which sodium is no longer drawn into or out of the cell). As the membrane potential becomes more positive, the sodium channels then close and lock, this is known as the "inactivated" state. During this state the channels cannot be opened regardless of the strength of the excitatory stimulus—this gives rise to the absolute refractory period. The relative refractory period is due to the leaking of potassium ions, which makes the membrane potential more negative (i.e. it is hyperpolarised), this resets the sodium channels; opening the inactivation gate, but still leaving the channel closed. Because some of the voltage-gated sodium ion channels have recovered and the voltage-gated potassium ion channels remain open, it is possible to initiate another action potential if the stimulus is stronger than a stimulus which can fire an action potential when the membrane is at rest.
554:, which allow Cl to enter the cell. Increased calcium concentration in the cell also increases activity of the sodium-calcium exchangers, while increased sodium concentration (from the depolarisation of phase 0) increases activity of the sodium-potassium pumps. The movement of all these ions results in the membrane potential remaining relatively constant, with K outflux, Cl influx as well as Na/K pumps contributing to repolarisation and Ca influx as well as Na/Ca exchangers contributing to depolarisation. This phase is responsible for the large duration of the action potential and is important in preventing irregular heartbeat (cardiac arrhythmia).
70:
326:
31:
1383:
1219:
1269:
or
Purkinje fibres reach the threshold potential for an action potential, they are depolarized by the oncoming impulse from the SAN This is called "overdrive suppression". Pacemaker activity of these cells is vital, as it means that if the SAN were to fail, then the heart could continue to beat, albeit at a lower rate (AVN= 40-60 beats per minute, Purkinje fibres = 20-40 beats per minute). These pacemakers will keep a patient alive until the emergency team arrives.
1070:
increases, these channels then close and lock (become inactive). Due to the rapid influx sodium ions (steep phase 0 in action potential waveform) activation and inactivation of these channels happens almost at exactly the same time. During the inactivation state, Na cannot pass through (absolute refractory period). However they begin to recover from inactivation as the membrane potential becomes more negative (relative refractory period).
1029:. Figure 3 shows the important ion channels involved in the cardiac action potential, the current (ions) that flows through the channels, their main protein subunits (building blocks of the channel), some of their controlling genes that code for their structure, and the phases that are active during the cardiac action potential. Some of the most important ion channels involved in the cardiac action potential are described briefly below.
484:(approximately −70 mV) it causes the Na channels to open. This produces a larger influx of sodium into the cell, rapidly increasing the voltage further to around +50 mV, i.e. towards the Na equilibrium potential. However, if the initial stimulus is not strong enough, and the threshold potential is not reached, the rapid sodium channels will not be activated and an action potential will not be produced; this is known as the
1051:). These poorly selective, cation (positively charged ions) channels conduct more current as the membrane potential becomes more negative (hyperpolarised). The activity of these channels in the SAN cells causes the membrane potential to depolarise slowly and so they are thought to be responsible for the pacemaker potential. Sympathetic nerves directly affect these channels, resulting in an increased heart rate (see below).
547:) allow potassium to leave the cell while L-type calcium channels (activated by the influx of sodium during phase 0) allow the movement of calcium ions into the cell. These calcium ions bind to and open more calcium channels (called ryanodine receptors) located on the sarcoplasmic reticulum within the cell, allowing the flow of calcium out of the SR. These calcium ions are responsible for the contraction of the heart.
342:
636:, the first from the beginning of phase 0 until part way through phase 3; this is known as the absolute refractory period during which it is impossible for the cell to produce another action potential. This is immediately followed, until the end of phase 3, by a relative refractory period, during which a stronger-than-usual stimulus is required to produce another action potential.
1370:(I for inhibitory), which is made up of 3 subunits (α, β and γ) which, when activated, separate from the receptor. The β and γ subunits activate a special set of potassium channels, increasing potassium flow out of the cell and decreasing membrane potential, meaning that the pacemaker cells take longer to reach their threshold value. The G
429:. These channels open at very negative voltages (i.e. immediately after phase 3 of the previous action potential; see below) and allow the passage of both K and Na into the cell. Due to their unusual property of being activated by very negative membrane potentials, the movement of ions through the HCN channels is referred to as the
62:. They produce roughly 60–100 action potentials every minute. The action potential passes along the cell membrane causing the cell to contract, therefore the activity of the sinoatrial node results in a resting heart rate of roughly 60–100 beats per minute. All cardiac muscle cells are electrically linked to one another, by
1331:). cAMP binds to the HCN channels (see above), increasing the funny current and therefore increasing the rate of depolarization, during the pacemaker potential. The increased cAMP also increases the opening time of L -type calcium channels, increasing the Ca current through the channel, speeding up phase 0.
372:
electrical gradient, for they represent a net displacement of charges across the membrane, which are unable to immediately re-enter the cell to restore the electrical equilibrium. Therefore, their slow re-entrance in the cell needs to be counterbalanced or the cell would slowly lose its membrane potential.
683:
at peak depolarization causes the conduction of cell to cell depolarization, not potassium.) These connections allow for the rapid conduction of the action potential throughout the heart and are responsible for allowing all of the cells in the atria to contract together as well as all of the cells in
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In addition to the SAN, the AVN and
Purkinje fibres also have pacemaker activity and can therefore spontaneously generate an action potential. However, these cells usually do not depolarize spontaneously, simply because action potential production in the SAN is faster. This means that before the AVN
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Ion channels are proteins that change shape in response to different stimuli to either allow or prevent the movement of specific ions across a membrane. They are said to be selectively permeable. Stimuli, which can either come from outside the cell or from within the cell, can include the binding of
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affecting the cardiac action potential. The sharp rise in voltage ("0") corresponds to the influx of sodium ions, whereas the two decays ("1" and "3", respectively) correspond to the sodium-channel inactivation and the repolarizing efflux of potassium ions. The characteristic plateau ("2") results
678:
of proteins, that form a pore through which ions (including Na, Ca and K) can pass. As potassium is highest within the cell, it is mainly potassium that passes through. This increased potassium in the neighbour cell causes the membrane potential to increase slightly, activating the sodium channels
444:
resulting in the increase in membrane potential (as a +3 charge is being brought into the cell (by the 3Na) but only a +2 charge is leaving the cell (by the Ca) therefore there is a net charge of +1 entering the cell). This calcium is then pumped back into the cell and back into the SR via calcium
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are voltage-dependent, opening rapidly due to depolarization of the membrane, which usually occurs from neighboring cells, through gap junctions. They allow for a rapid flow of sodium into the cell, depolarizing the membrane completely and initiating an action potential. As the membrane potential
375:
The second purpose, intricately linked to the first, is to keep the intracellular concentration more or less constant, and in this case to re-establish the original chemical gradients, that is to force the sodium and calcium which previously flowed into the cell out of it, and the potassium which
371:
serve two purposes. The first is to maintain the existence of the resting membrane potential by countering the depolarisation due to the leakage of ions not at the electrochemical equilibrium (e.g. sodium and calcium). These ions not being at the equilibrium is the reason for the existence of an
1209:
These channels respond to voltage changes across the membrane differently: L-type channels are activated by more positive membrane potentials, take longer to open and remain open longer than T-type channels. This means that the T-type channels contribute more to depolarization (phase 0) whereas
1152:
Another form of voltage-gated potassium channels are the delayed rectifier potassium channels. These channels carry potassium currents which are responsible for the plateau phase of the action potential, and are named based on the speed at which they activate: slowly activating
512:(phase 4) or an oncoming action potential. The L-type calcium channels are activated more slowly than the sodium channels, therefore, the depolarization slope in the pacemaker action potential waveform is less steep than that in the non-pacemaker action potential waveform.
363:
results from the flux of ions having flowed into the cell (e.g. sodium and calcium), the flux of ions having flowed out of the cell (e.g. potassium, chloride and bicarbonate), as well as the flux of ions generated by the different membrane pumps, being perfectly balanced.
224:
is around −90 millivolts (mV; 1 mV = 0.001 V), i.e. the inside of the membrane is more negative than the outside. The main ions found outside the cell at rest are sodium (Na), and chloride (Cl), whereas inside the cell it is mainly potassium (K).
376:
previously flowed out of the cell back into it (though as the potassium is mostly at the electrochemical equilibrium, its chemical gradient will naturally reequilibrate itself opposite to the electrical gradient, without the need for an active transport mechanism).
345:
Figure 2a: Ventricular action potential (left) and sinoatrial node action potential (right) waveforms. The main ionic currents responsible for the phases are below (upwards deflections represent ions flowing out of cell, downwards deflection represents inward
616:
restore ion concentrations back to balanced states pre-action potential. This means that the intracellular calcium is pumped out, which was responsible for cardiac myocyte contraction. Once this is lost, the contraction stops and the heart muscles relax.
422:. During this phase, the membrane potential slowly becomes more positive, until it reaches a set value (around -40 mV; known as the threshold potential) or until it is depolarized by another action potential, coming from a neighboring cell.
1280:, where the signal from the SAN is impaired in its path to the ventricles. This leads to uncoordinated contractions between the atria and ventricles, without the correct delay in between and in severe cases can result in sudden death.
337:
The standard model used to understand the cardiac action potential is that of the ventricular myocyte. Outlined below are the five phases of the ventricular myocyte action potential, with reference also to the SAN action potential.
85:(ECG). This is a series of upward and downward spikes (labelled P, Q, R, S and T) that represent the depolarization (voltage becoming more positive) and repolarization (voltage becoming more negative) of the action potential in the
402:
During this phase the membrane is most permeable to K, which can travel into or out of cell through leak channels, including the inwardly rectifying potassium channel. Therefore, the resting membrane potential is mostly equal to K
601:. This net outward, positive current (equal to loss of positive charge from the cell) causes the cell to repolarize. The delayed rectifier K channels close when the membrane potential is restored to about -85 to -90 mV, while I
2531:
Lacerda, AE; Kim, HS; Ruth, P; Perez-Reyes, E; et al. (August 1991). "Normalization of current kinetics by interaction between the alpha 1 and beta subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel".
1006:) and can act to open or close the channel. The pore formed by an ion channel is aqueous (water-filled) and allows the ion to rapidly travel across the membrane. Ion channels can be selective for specific ions, so there are
496:
also constitutes a minor part of the depolarisation effect. The slope of phase 0 on the action potential waveform (see figure 2) represents the maximum rate of voltage change of the cardiac action potential and is known as
1106:
is responsible for maintaining the resting membrane potential and initiating the depolarization phase. However, as the membrane potential continues to become more positive, the channel begins to allow the passage of K
2636:
Hibino, Hiroshi; Inanobe, Atsushi; Furutani, Kazuharu; Murakami, Shingo; Findlay, Ian; Kurachi, Yoshihisa (2010-01-01). "Inwardly rectifying potassium channels: their structure, function, and physiological roles".
1046:
are located mainly in pacemaker cells, these channels become active at very negative membrane potentials and allow for the passage of both Na and K into the cell (which is a movement known as a funny current,
524:) open and close rapidly, allowing for a brief flow of potassium ions out of the cell, making the membrane potential slightly more negative. This is referred to as a 'notch' on the action potential waveform.
508:), however, the increase in membrane voltage is mainly due to activation of L-type calcium channels. These channels are also activated by an increase in voltage, however this time it is either due to the
2583:
Purves, Dale; Augustine, George J.; Fitzpatrick, David; Katz, Lawrence C.; LaMantia, Anthony-Samuel; McNamara, James O.; Williams, S. Mark (2001-01-01). "The
Molecular Structure of Ion Channels".
520:
This phase begins with the rapid inactivation of the Na channels by the inner gate (inactivation gate), reducing the movement of sodium into the cell. At the same time potassium channels (called I
2285:
Clark RB, Mangoni ME, Lueger A, Couette B, Nargeot J, Giles WR (May 2004). "A rapidly activating delayed rectifier K+ current regulates pacemaker activity in adult mouse sinoatrial node cells".
2242:
Kubo, Y; Adelman, JP; Clapham, DE; Jan, LY; et al. (2005). "International Union of
Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels".
620:
In the sinoatrial node, this phase is also due to the closure of the L-type calcium channels, preventing inward flux of Ca and the opening of the rapid delayed rectifier potassium channels (I
1882:
Santana, L.F., Cheng, E.P. and
Lederer, J.W. (2010a) 'How does the shape of the cardiac action potential control calcium signaling and contraction in the heart?', 49(6).
3066:
Demir, Semahat S.; Clark, John W.; Giles, Wayne R. (1999-06-01). "Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart: a unifying model".
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for K (~-90 mV). As the membrane potential becomes more positive (i.e. during cell stimulation from a neighbouring cell), the flow of potassium into the cell via the K
244:), the action potential terminates as potassium channels open, allowing K to leave the cell and causing the membrane potential to return to negative, this is known as
539:
remaining almost constant, as the membrane slowly begins to repolarize. This is due to the near balance of charge moving into and out of the cell. During this phase
3015:
Osterrieder, W.; Noma, A.; Trautwein, W. (1980-07-01). "On the kinetics of the potassium channel activated by acetylcholine in the S-A node of the rabbit heart".
208:
Although intracellular Ca content is about 2 mM, most of this is bound or sequestered in intracellular organelles (mitochondria and sarcoplasmic reticulum).
66:
which allow the action potential to pass from one cell to the next. This means that all atrial cells can contract together, and then all ventricular cells.
1276:. Sustained training of athletes causes a cardiac adaptation where the resting SAN rate is lower (sometimes around 40 beats per minute). This can lead to
3287:
283:
expressed and mechanisms by which they are activated results in differences in the configuration of the action potential waveform, as shown in figure 2.
1712:"Impact of Sarcoplasmic Reticulum Calcium Release on Calcium Dynamics and Action Potential Morphology in Human Atrial Myocytes: A Computational Study"
2688:
Dhamoon, Amit S.; Jalife, José (2005-03-01). "The inward rectifier current (IK1) controls cardiac excitability and is involved in arrhythmogenesis".
1257:. This delay allows the ventricles to fully fill with blood before contraction. The signal then passes down through a bundle of fibres called the
77:
Rate dependence of the action potential is a fundamental property of cardiac cells and alterations can lead to severe cardiac diseases including
2175:
2203:"Repolarization of the cardiac action potential. Does an increase in repolarization capacity constitute a new anti-arrhythmic principle?"
1929:"Repolarization of the cardiac action potential. Does an increase in repolarization capacity constitute a new anti-arrhythmic principle?"
1127:
17:
1769:
Issa ZF, Miller JM, Zipes DP (2019). "Electrophysiological
Mechanisms of Cardiac Arrhythmias: Abnormal Automaticity". In Issa ZF (ed.).
1437:
Zhao, G; Qiu, Y; Zhang, HM; Yang, D (January 2019). "Intercalated discs: cellular adhesion and signaling in heart health and diseases".
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network, the fastest conduction pathway within the heart. The electrical signal travels from the sinoatrial node, which stimulates the
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favour the flow of K into the cell. This influx of potassium, however, is larger when the membrane potential is more negative than the
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remain open as more potassium leak channels open. This ensures a net outward positive current, corresponding to negative change in
46:, the cardiac action potential is not initiated by nervous activity. Instead, it arises from a group of specialized cells known as
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of the heart to generate spontaneous cardiac action potentials. Automaticity can be normal or abnormal, caused by temporary
1359:
329:
Action potentials recorded from sheep atrial and ventricular cardiomyocytes with phases shown. Ion currents approximate to
2956:
DiFrancesco, D.; Tortora, P. (1991-05-09). "Direct activation of cardiac pacemaker channels by intracellular cyclic AMP".
275:, that spontaneously generate the cardiac action potential and those non-pacemaker cells that simply conduct it, such as
1025:
Each channel is coded by a set of DNA instructions that tell the cell how to make it. These instructions are known as a
3879:
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1126:) are activated by depolarization. The currents produced by these channels include the transient out potassium current
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The two main types of potassium channels in cardiac cells are inward rectifiers and voltage-gated potassium channels.
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256:(SR) where calcium is stored, and is also found outside of the cell. Release of Ca from the SR, via a process called
359:. In the standard non-pacemaker cell the voltage during this phase is more or less constant, at roughly -90 mV. The
309:
characteristic changes such as certain medication usage, or in the case of abnormal automaticity the changes are in
3228:
2829:
Tsien, R. W.; Carpenter, D. O. (1978-06-01). "Ionic mechanisms of pacemaker activity in cardiac
Purkinje fibers".
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257:
1374:-protein also inhibits the cAMP pathway therefore reducing the sympathetic effects caused by the spinal nerves.
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1324:
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and initiating an action potential in this cell. (A brief chemical gradient driven efflux of Na+ through the
1663:"How does the shape of the cardiac action potential control calcium signaling and contraction in the heart?"
3800:
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1194:('T' for Transient, i.e. short). L-type channels are more common and are most densely populated within the
480:. When this happens, the voltage within the cell increases slightly. If this increased voltage reaches the
330:
260:, is vital for the plateau phase of the action potential (see phase 2, below) and is a fundamental step in
1111:
of the cell. This outward flow of potassium ions at the more positive membrane potentials means that the K
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the ventricles. Uncoordinated contraction of heart muscles is the basis for arrhythmia and heart failure.
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Another hypothesis regarding the pacemaker potential is the 'calcium clock'. Calcium is released from the
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specific channels. They can also be specific for a certain charge of ions (i.e. positive or negative).
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50:, that have automatic action potential generation capability. In healthy hearts, these cells form the
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In non-pacemaker cells (i.e. ventricular cells), this is produced predominantly by the activation of
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and sometimes sudden death. Action potential activity within the heart can be recorded to produce an
3643:
3633:
1892:
Morad M., Tung L. (1982). "Ionic events responsible for the cardiac resting and action potential".
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The speed of action potential production in pacemaker cells is affected, but not controlled by the
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476:). These channels are activated when an action potential arrives from a neighbouring cell, through
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1149:. These currents contribute to the early repolarization phase (phase 1) of the action potential.
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1346:), by increasing the time taken to produce an action potential in the SAN. A nerve called the
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1002:) or a change in membrane potential around the channel, detected by a sensor (also known as
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3348:
3122:
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2870:
2541:
2518:"SCN5A sodium channel, voltage-gated, type V, alpha subunit [Homo sapiens (human)]"
2146:. Boron, Walter F.,, Boulpaep, Emile L. (Updated ed.). Philadelphia, PA. p. 508.
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In the ventricular myocyte, phase 4 occurs when the cell is at rest, in a period known as
8:
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allow the action potential to be transferred from one cell to the next (they are said to
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remains conducting throughout phase 4, which helps to set the resting membrane potential
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481:
419:
3126:
3113:
Rudy, Yoram (March 2008). "Molecular Basis of
Cardiac Action Potential Repolarization".
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1323:-protein (s for stimulatory). Activation of this G-protein leads to increased levels of
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Clinical arrhythmology and electrophysiology: a companion to
Braunwald's heart disease
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that are too fast. Other drugs used to influence the cardiac action potential include
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During phase 3 (the "rapid repolarization" phase) of the action potential, the L-type
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The action potential begins with the voltage becoming more positive; this is known as
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1307:), by decreasing the time to produce an action potential in the SAN. Nerves from the
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This phase consists of a rapid, positive change in voltage across the cell membrane (
276:
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82:
63:
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The pacemaker potential is thought to be due to a group of channels, referred to as
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membrane of ventricular cells, whereas the T-type channels are found mainly within
1015:
671:
408:
395:) to move three Na out of the cell and two K into the cell. Another example is the
39:
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1989:
1972:
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which binds to a receptor located on the outside of the pacemaker cell, called an
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dominant while the body is resting and digesting) decreases heart rate (negative
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of the cell, during phase 0, causes the membrane potential to approach sodium's
3815:
3740:
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3326:
3313:
2650:
2584:
2022:"The role of the calcium and the voltage clocks in sinoatrial node dysfunction"
1819:
1315:, which binds to and activates receptors on the pacemaker cell membrane called
1312:
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648:
640:
458:
302:
245:
233:
229:
86:
59:
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3121:(Control and Regulation of Transport Phenomena in the Cardiac System): 113–8.
2462:
Severs, Nicholas J. (2002-12-01). "Gap junction remodeling in heart failure".
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Different shapes of the cardiac action potential in various parts of the heart
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1253:, which slows down conduction of the action potential from the atria to the
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Hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels)
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1913:
1533:"Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice"
1350:, that begins in the brain and travels to the sinoatrial node, releases a
585:, thus allowing more types of K channels to open. These are primarily the
3852:
3842:
3570:
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3560:
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2517:
1347:
1308:
1135:. This current has two components. Both components activate rapidly, but
1043:
1038:
426:
306:
108:
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Purves, D; Augustine, GJ; Fitzpatrick, D; Hall, WC; et al. (2008).
461:) lasting less than 2 ms in ventricular cells and 10–20 ms in
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3575:
3465:
3448:
3331:
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2255:
1661:
Santana, Luis F.; Cheng, Edward P.; Lederer, W. Jonathan (2010-12-01).
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Soltysinska E, Speerschneider T, Winther SV, Thomsen MB (August 2014).
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cells. This occurs due to a net flow of positive charge into the cell.
78:
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at the bottom (apex) of the heart, causing ventricular contraction.
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These two refractory periods are caused by changes in the states of
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680:
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356:
2866:"The relationship among cardiac pacemakers: Overdrive suppression"
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There is no plateau phase present in pacemaker action potentials.
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HCN channels (Hyperpolarization-activated cyclic nucleotide-gated)
3745:
1482:"Gap junction modulation and its implications for heart function"
769:
489:
3068:
American
Journal of Physiology. Heart and Circulatory Physiology
2287:
American Journal of Physiology. Heart and Circulatory Physiology
2123:
418:
are never at rest. In these cells, phase 4 is also known as the
3585:
3580:
3262:
of cardiac action potential and other generic action potentials
1272:
An example of premature ventricular contraction is the classic
929:
895:
570:
540:
440:
within the cell. This calcium then increases activation of the
399:
which removes one Ca from the cell for three Na into the cell.
380:
341:
237:
2582:
2331:
2111:
1773:(Third ed.). Philadelphia, PA: Elsevier. pp. 51–80.
1710:
Koivumäki, Jussi T.; Korhonen, Topi; Tavi, Pasi (2011-01-01).
696:
Major currents during the cardiac ventricular action potential
3717:
3304:
2635:
1339:
1283:
899:
891:
861:
829:
801:
797:
741:
446:
112:
3295:
2313:
2144:
Medical physiology : a cellular and molecular approach
1026:
855:
586:
535:
This phase is also known as the "plateau" phase due to the
2498:
472:, which increases the membrane conductance (flow) of Na (g
267:
There are important physiological differences between the
3256:
illustrating the generation of a cardiac action potential
2617:
2530:
2284:
1479:
104:
3014:
527:
There is no obvious phase 1 present in pacemaker cells.
2361:
2182:
1801:
220:(voltage when the cell is not electrically excited) of
2733:"Structure and function of cardiac potassium channels"
1600:
10.2344/0003-3006(2006)53[53:foei]2.0.co;2
1973:"The role of the funny current in pacemaker activity"
1709:
1210:
L-type channels contribute to the plateau (phase 2).
1206:, but still to a lesser degree than L-type channels.
3225:
Medical Physiology: Principles for Clinical Medicine
3208:(4th ed.). Sunderland, MA: Sinauer Associates.
2405:
Goodenough, Daniel A.; Paul, David L. (2009-07-01).
2194:
1966:
1964:
1804:"Overview of Basic Mechanisms of Cardiac Arrhythmia"
1584:"Fundamentals of Electrocardiography Interpretation"
1660:
240:to flow into the cell. After a delay (known as the
3222:
2955:
2336:
2129:
1261:, located between the ventricles, and then to the
1961:
1891:
1656:
1654:
1115:can also aid the final stages of repolarisation.
550:Calcium also activates chloride channels called I
3871:
2520:. National Center for Biotechnology Information.
1436:
3065:
3017:Pflügers Archiv: European Journal of Physiology
2325:
1768:
1581:
2828:
2404:
2071:"Anatomy of the action potential in the heart"
1878:
1876:
1874:
1872:
1853:"Cardiac Arrhythmias - Textbook of Cardiology"
1651:
3281:
3203:
2687:
2319:
2142:Boron, Walter F.; Boulpaep, Emile L. (2012).
2141:
2117:
1233:electrical activity that originates from the
2857:
2278:
2019:
2013:
1802:Antzelevitch C, Burashnikov A (March 2011).
1667:Journal of Molecular and Cellular Cardiology
1480:Kurtenbach S, Kurtenbach S, Zoidl G (2014).
998:to a receptor on the channel (also known as
279:). The specific differences in the types of
252:, which can be found inside the cell in the
2524:
2241:
1970:
1869:
1624:
1524:
1473:
3288:
3274:
3115:Annals of the New York Academy of Sciences
2411:Cold Spring Harbor Perspectives in Biology
2200:
2174:: CS1 maint: location missing publisher (
1284:Regulation by the autonomic nervous system
1054:
2932:
2883:
2797:
2748:
2438:
2384:. Cover Publishing Company. p. 145.
2218:
2094:
2045:
1988:
1944:
1926:
1827:
1745:
1735:
1686:
1607:
1558:
1548:
1507:
1497:
1224:electrical conduction system of the heart
608:Ionic pumps as discussed above, like the
3180:
3157:
2906:
2863:
2623:
2504:
2367:
2235:
2188:
1381:
1377:
1217:
340:
324:
205:
68:
29:
3297:Physiology of the cardiovascular system
3183:Human Physiology, From Cells to Systems
3160:Human Physiology, From Cells to Systems
2779:
2730:
2382:Ion Adventure in the Heartland Volume 1
2020:Joung B, Chen PS, Lin SF (March 2011).
1637:(5th ed.). Springer. p. 150.
286:
262:cardiac excitation-contraction coupling
14:
3872:
3223:Rhoades, R.; Bell, D.R., eds. (2009).
2461:
1390:from the opening of voltage-sensitive
1319:. This activates a protein, called a G
1088:Inwardly rectifying potassium channels
3269:
2379:
1073:
409:Goldman-Hodgkin-Katz voltage equation
298:, is the property of the specialized
3112:
2068:
1630:
1213:
627:
541:delayed rectifier potassium channels
232:and is mainly due to the opening of
2343:. New York: W. H. Freeman. p.
1430:
1299:(nerves dominant during the body's
1177:
103:Figure 1: Intra- and extracellular
24:
2782:"A tale of two (Calcium) channels"
1894:The American Journal of Cardiology
1779:10.1016/B978-0-323-52356-1.00003-7
391:which uses energy (in the form of
25:
3896:
3247:
3229:Lippincott Williams & Wilkins
3080:10.1152/ajpheart.1999.276.6.H2221
2599:
2335:; Orkand, R; Grinnell, A (1977).
1971:DiFrancesco, Dario (2010-02-19).
1808:Cardiac Electrophysiology Clinics
2220:10.1111/j.1748-1716.2009.02072.x
1946:10.1111/j.1748-1716.2009.02072.x
1850:
1303:) increase heart rate (positive
1120:voltage-gated potassium channels
658:
407:and can be calculated using the
216:Similar to skeletal muscle, the
3260:Interactive mathematical models
3105:
3059:
3008:
2949:
2900:
2822:
2773:
2724:
2681:
2629:
2593:
2576:
2510:
2455:
2398:
2373:
2339:Introduction to Nervous Systems
2135:
2062:
1920:
1885:
1844:
1032:
691:
258:calcium-induced calcium release
27:Biological process in the heart
1795:
1762:
1703:
1634:Principles of Renal Physiology
1575:
1336:parasympathetic nervous system
1184:voltage-gated calcium channels
1142:inactivates more rapidly than
34:Basic cardiac action potential
13:
1:
3424:Aortic valve area calculation
2750:10.1016/s0008-6363(99)00071-1
2731:Snyders, D. J. (1999-05-01).
2075:Texas Heart Institute Journal
1990:10.1161/CIRCRESAHA.109.208041
1906:10.1016/s0002-9149(82)80016-7
1424:
1167:and ultra-rapidly activating
2602:"Ion channels and receptors"
1857:www.textbookofcardiology.org
1737:10.1371/journal.pcbi.1001067
1237:(SAN) is propagated via the
393:adenosine triphosphate (ATP)
331:ventricular action potential
7:
3541:Effective refractory period
3420:) / End-diastolic dimension
2702:10.1016/j.hrthm.2004.11.012
2423:10.1101/cshperspect.a002576
2299:10.1152/ajpheart.00753.2003
1679:10.1016/j.yjmcc.2010.09.005
1251:atrioventricular node (AVN)
1190:('L' for Long-lasting) and
687:
387:ions are maintained by the
248:. Another important ion is
96:
18:Cardiac muscle automaticity
10:
3901:
2780:Nargeot, J. (2000-03-31).
2651:10.1152/physrev.00021.2009
2464:Journal of Cardiac Failure
1820:10.1016/j.ccep.2010.10.012
1716:PLOS Computational Biology
1537:Cardiovascular Diabetology
1415:potassium channel blockers
1311:release a molecule called
1297:sympathetic nervous system
1077:
1058:
1036:
1004:voltage-gated ion channels
674:). They are made from the
560:
530:
515:
452:
361:resting membrane potential
350:
313:, caused, for example, by
242:absolute refractory period
218:resting membrane potential
3880:Cardiac electrophysiology
3826:Tubuloglomerular feedback
3781:
3773:Critical closing pressure
3731:
3698:
3684:
3664:
3601:
3593:Hexaxial reference system
3516:Cardiac electrophysiology
3503:
3447:
3399:
3312:
3303:
2038:10.3349/ymj.2011.52.2.211
1550:10.1186/s12933-014-0122-y
1451:10.1007/s10741-018-9743-7
1231:heart's conduction system
1000:ligand-gated ion channels
504:In pacemaker cells (e.g.
320:
3801:Renin–angiotensin system
2925:10.1136/heart.89.12.1455
2476:10.1054/jcaf.2002.129255
2069:Shih, H T (1994-01-01).
1582:Becker Daniel E (2006).
1499:10.3389/fphys.2014.00082
1419:calcium channel blockers
1301:fight-or-flight response
1290:autonomic nervous system
717:
714:
711:
704:
702:
610:sodium-calcium exchanger
442:sodium-calcium exchanger
397:sodium-calcium exchanger
311:electrotonic environment
132:
129:
126:
123:
120:
3831:Cerebral autoregulation
3796:Kinin–kallikrein system
3763:Jugular venous pressure
3413:End-diastolic dimension
3391:Pressure volume diagram
3135:10.1196/annals.1420.013
2907:Fagard R (2003-12-01).
2885:10.1161/01.res.41.3.269
2799:10.1161/01.res.86.6.613
2737:Cardiovascular Research
2130:Rhoades & Bell 2009
1486:Frontiers in Physiology
1407:sodium channel blockers
1274:athletic heart syndrome
1192:T-type calcium channels
1188:L-type calcium channels
1186:within cardiac muscle:
1102:decreases. Therefore, K
1055:The fast sodium channel
632:Cardiac cells have two
587:rapid delayed rectifier
494:L-type calcium channels
3768:Portal venous pressure
3758:Mean arterial pressure
3672:Ventricular remodeling
3418:End-systolic dimension
3376:Cardiac function curve
2831:Federation Proceedings
2026:Yonsei Medical Journal
1395:
1360:M2 muscarinic receptor
1278:atrioventricular block
1226:
978:Ca-transporting ATPase
571:slow delayed rectifier
438:sarcoplasmic reticulum
367:The activity of these
347:
334:
254:sarcoplasmic reticulum
74:
35:
3409:Fractional shortening
3254:Interactive animation
3181:Sherwood, L. (2012).
3158:Sherwood, L. (2008).
2864:Vassalle, M. (1977).
2639:Physiological Reviews
2470:(6 Suppl): S293–299.
1439:Heart Failure Reviews
1401:are used to regulate
1385:
1378:Clinical significance
1327:in the cell (via the
1221:
1160:, rapidly activating
1096:equilibrium potential
653:equilibrium potential
614:sodium-potassium pump
506:sinoatrial node cells
445:pumps (including the
405:equilibrium potential
389:sodium-potassium pump
344:
328:
315:myocardial infarction
72:
54:and are found in the
44:skeletal muscle cells
33:
3349:End-diastolic volume
2871:Circulation Research
2786:Circulation Research
1977:Circulation Research
1399:Antiarrhythmic drugs
1249:to contract, to the
292:Cardiac automaticity
287:Cardiac automaticity
277:ventricular myocytes
3713:Vascular resistance
3551:Electrocardiography
3546:Pacemaker potential
3476:Conduction velocity
3381:Venous return curve
3354:End-systolic volume
3127:2008NYASA1123..113R
2970:1991Natur.351..145D
2546:1991Natur.352..527L
2201:Grunnet M (2010b).
1728:2011PLSCB...7E1067K
1588:Anesthesia Progress
1362:. This activates a
1356:acetylcholine (ACh)
699:
668:electrically couple
595:inwardly rectifying
510:pacemaker potential
482:threshold potential
420:pacemaker potential
117:
3821:Myogenic mechanism
3439:Left atrial volume
3371:Frank–Starling law
3074:(6): H2221–H2244.
3029:10.1007/bf00584196
2507:, pp. 248–50.
2320:Purves et al. 2008
2256:10.1124/pr.57.4.11
2118:Purves et al. 2008
1927:Grunnet M (2010).
1396:
1227:
1074:Potassium channels
712:α subunit protein
692:
645:potassium channels
634:refractory periods
583:membrane potential
537:membrane potential
348:
335:
101:
79:cardiac arrhythmia
75:
64:intercalated discs
36:
3885:Action potentials
3867:
3866:
3863:
3862:
3680:
3679:
3520:Action potential
3511:Conduction system
3457:Cardiac pacemaker
3429:Ejection fraction
3185:(8th ed.).
2964:(6322): 145–147.
2909:"Athlete's heart"
2626:, pp. 310–1.
2391:978-0-912912-11-0
2207:Acta Physiologica
2120:, pp. 26–28.
1933:Acta Physiologica
1788:978-0-323-52356-1
1631:Lote, C. (2012).
1214:Conduction system
1080:Potassium channel
991:
990:
921:3Na-1Ca-exchanger
698:
628:Refractory period
569:close, while the
379:For example, the
222:ventricular cells
214:
213:
83:electrocardiogram
52:cardiac pacemaker
16:(Redirected from
3892:
3806:Vasoconstrictors
3783:Regulation of BP
3696:
3695:
3629:pulmonary artery
3602:Chamber pressure
3310:
3309:
3290:
3283:
3276:
3267:
3266:
3242:
3219:
3200:
3187:Cengage Learning
3177:
3164:Cengage Learning
3162:(7th ed.).
3154:
3100:
3099:
3063:
3057:
3056:
3012:
3006:
3005:
2978:10.1038/351145a0
2953:
2947:
2946:
2936:
2904:
2898:
2897:
2887:
2861:
2855:
2854:
2837:(8): 2127–2131.
2826:
2820:
2819:
2801:
2777:
2771:
2770:
2752:
2728:
2722:
2721:
2685:
2679:
2678:
2633:
2627:
2621:
2615:
2614:
2612:
2611:
2606:
2597:
2591:
2590:
2580:
2574:
2573:
2554:10.1038/352527a0
2540:(6335): 527–30.
2528:
2522:
2521:
2514:
2508:
2502:
2496:
2495:
2459:
2453:
2452:
2442:
2402:
2396:
2395:
2377:
2371:
2365:
2359:
2358:
2342:
2329:
2323:
2317:
2311:
2310:
2282:
2276:
2275:
2239:
2233:
2232:
2222:
2198:
2192:
2186:
2180:
2179:
2173:
2165:
2139:
2133:
2127:
2121:
2115:
2109:
2108:
2098:
2066:
2060:
2059:
2049:
2017:
2011:
2010:
1992:
1968:
1959:
1958:
1948:
1924:
1918:
1917:
1889:
1883:
1880:
1867:
1866:
1864:
1863:
1848:
1842:
1841:
1831:
1799:
1793:
1792:
1766:
1760:
1759:
1749:
1739:
1707:
1701:
1700:
1690:
1658:
1649:
1648:
1628:
1622:
1621:
1611:
1579:
1573:
1572:
1562:
1552:
1528:
1522:
1521:
1511:
1501:
1477:
1471:
1470:
1434:
1392:calcium channels
1317:β1 adrenoceptors
1178:Calcium channels
987:ion homeostasis
961:ion homeostasis
935:ion homeostasis
700:
697:
488:. The influx of
210:
118:
107:concentrations (
100:
40:action potential
21:
3900:
3899:
3895:
3894:
3893:
3891:
3890:
3889:
3870:
3869:
3868:
3859:
3777:
3727:
3689:
3686:Vascular system
3676:
3660:
3597:
3499:
3484:(Contractility)
3443:
3395:
3386:Wiggers diagram
3299:
3294:
3250:
3245:
3239:
3216:
3197:
3174:
3108:
3103:
3064:
3060:
3013:
3009:
2954:
2950:
2919:(12): 1455–61.
2905:
2901:
2862:
2858:
2827:
2823:
2778:
2774:
2729:
2725:
2686:
2682:
2634:
2630:
2622:
2618:
2609:
2607:
2604:
2600:Sheng, Morgan.
2598:
2594:
2589:(2nd ed.).
2581:
2577:
2529:
2525:
2516:
2515:
2511:
2503:
2499:
2460:
2456:
2407:"Gap junctions"
2403:
2399:
2392:
2378:
2374:
2366:
2362:
2355:
2330:
2326:
2318:
2314:
2293:(5): H1757–66.
2283:
2279:
2240:
2236:
2199:
2195:
2187:
2183:
2167:
2166:
2154:
2140:
2136:
2128:
2124:
2116:
2112:
2067:
2063:
2018:
2014:
1969:
1962:
1925:
1921:
1890:
1886:
1881:
1870:
1861:
1859:
1849:
1845:
1800:
1796:
1789:
1767:
1763:
1722:(1): e1001067.
1708:
1704:
1659:
1652:
1645:
1629:
1625:
1580:
1576:
1529:
1525:
1478:
1474:
1435:
1431:
1427:
1380:
1373:
1367:
1322:
1286:
1263:Purkinje fibers
1235:sinoatrial node
1216:
1204:pacemaker cells
1180:
1173:
1166:
1159:
1148:
1141:
1133:
1125:
1114:
1105:
1101:
1093:
1082:
1076:
1067:sodium channels
1063:
1057:
1050:
1041:
1035:
974:
948:
917:
886:
879:
853:
847:
825:
819:
793:
787:
765:
759:
737:
731:
715:α subunit gene
690:
676:connexin family
661:
630:
623:
604:
600:
592:
576:
563:
553:
546:
533:
523:
518:
500:
486:all-or-none law
475:
455:
416:pacemaker cells
353:
323:
296:autorhythmicity
289:
273:sinoatrial node
269:pacemaker cells
234:sodium channels
206:
99:
56:sinoatrial node
48:pacemaker cells
28:
23:
22:
15:
12:
11:
5:
3898:
3888:
3887:
3882:
3865:
3864:
3861:
3860:
3858:
3857:
3856:
3855:
3850:
3845:
3835:
3834:
3833:
3828:
3823:
3816:Autoregulation
3813:
3808:
3803:
3798:
3793:
3787:
3785:
3779:
3778:
3776:
3775:
3770:
3765:
3760:
3755:
3754:
3753:
3748:
3741:Pulse pressure
3737:
3735:
3733:Blood pressure
3729:
3728:
3726:
3725:
3720:
3715:
3710:
3704:
3702:
3693:
3682:
3681:
3678:
3677:
3675:
3674:
3668:
3666:
3662:
3661:
3659:
3658:
3653:
3652:
3651:
3646:
3638:
3637:
3636:
3626:
3625:
3624:
3619:
3611:
3609:Central venous
3605:
3603:
3599:
3598:
3596:
3595:
3590:
3589:
3588:
3583:
3578:
3573:
3568:
3563:
3558:
3548:
3543:
3538:
3537:
3536:
3531:
3526:
3518:
3513:
3507:
3505:
3501:
3500:
3498:
3497:
3491:
3490:(Excitability)
3485:
3479:
3469:
3459:
3453:
3451:
3445:
3444:
3442:
3441:
3436:
3431:
3426:
3421:
3415:
3405:
3403:
3397:
3396:
3394:
3393:
3388:
3383:
3378:
3373:
3368:
3363:
3358:
3357:
3356:
3351:
3341:
3340:
3339:
3334:
3327:Cardiac output
3324:
3318:
3316:
3314:Cardiac output
3307:
3301:
3300:
3293:
3292:
3285:
3278:
3270:
3264:
3263:
3257:
3249:
3248:External links
3246:
3244:
3243:
3237:
3220:
3214:
3201:
3195:
3178:
3172:
3155:
3109:
3107:
3104:
3102:
3101:
3058:
3023:(2): 101–109.
3007:
2948:
2899:
2856:
2821:
2792:(6): 613–615.
2772:
2743:(2): 377–390.
2723:
2696:(3): 316–324.
2680:
2645:(1): 291–366.
2628:
2616:
2592:
2575:
2523:
2509:
2497:
2454:
2417:(1): a002576.
2397:
2390:
2380:Dubin (2003).
2372:
2370:, p. 316.
2360:
2354:978-0716700302
2353:
2324:
2312:
2277:
2234:
2193:
2191:, p. 311.
2181:
2152:
2134:
2122:
2110:
2061:
2012:
1983:(3): 434–446.
1960:
1919:
1900:(3): 584–594.
1884:
1868:
1843:
1794:
1787:
1761:
1702:
1673:(6): 901–903.
1650:
1643:
1623:
1574:
1523:
1472:
1445:(1): 115–132.
1428:
1426:
1423:
1379:
1376:
1371:
1365:
1320:
1285:
1282:
1215:
1212:
1182:There are two
1179:
1176:
1171:
1164:
1157:
1146:
1139:
1131:
1123:
1112:
1103:
1099:
1091:
1078:Main article:
1075:
1072:
1061:Sodium channel
1059:Main article:
1056:
1053:
1048:
1037:Main article:
1034:
1031:
989:
988:
985:
980:
975:
972:
967:
963:
962:
959:
954:
949:
946:
941:
937:
936:
933:
923:
918:
915:
910:
906:
905:
902:
889:
884:
880:
877:
872:
868:
867:
864:
859:
851:
848:
845:
840:
836:
835:
832:
827:
823:
820:
817:
812:
808:
807:
804:
795:
791:
788:
785:
780:
776:
775:
772:
767:
763:
760:
757:
752:
748:
747:
744:
739:
735:
732:
729:
724:
720:
719:
716:
713:
710:
703:
689:
686:
660:
657:
649:depolarization
629:
626:
621:
602:
598:
590:
574:
562:
559:
551:
544:
532:
529:
521:
517:
514:
498:
473:
459:depolarization
454:
451:
352:
349:
322:
319:
294:also known as
288:
285:
246:repolarization
230:depolarization
212:
211:
203:
202:
199:
196:
193:
190:
186:
185:
182:
179:
176:
173:
169:
168:
165:
162:
159:
156:
152:
151:
148:
145:
142:
139:
135:
134:
131:
130:Intracellular
128:
127:Extracellular
125:
122:
98:
95:
26:
9:
6:
4:
3:
2:
3897:
3886:
3883:
3881:
3878:
3877:
3875:
3854:
3851:
3849:
3846:
3844:
3841:
3840:
3839:
3836:
3832:
3829:
3827:
3824:
3822:
3819:
3818:
3817:
3814:
3812:
3809:
3807:
3804:
3802:
3799:
3797:
3794:
3792:
3789:
3788:
3786:
3784:
3780:
3774:
3771:
3769:
3766:
3764:
3761:
3759:
3756:
3752:
3749:
3747:
3744:
3743:
3742:
3739:
3738:
3736:
3734:
3730:
3724:
3721:
3719:
3716:
3714:
3711:
3709:
3706:
3705:
3703:
3701:
3697:
3694:
3692:
3687:
3683:
3673:
3670:
3669:
3667:
3663:
3657:
3654:
3650:
3647:
3645:
3642:
3641:
3639:
3635:
3632:
3631:
3630:
3627:
3623:
3620:
3618:
3615:
3614:
3612:
3610:
3607:
3606:
3604:
3600:
3594:
3591:
3587:
3584:
3582:
3579:
3577:
3574:
3572:
3569:
3567:
3564:
3562:
3559:
3557:
3554:
3553:
3552:
3549:
3547:
3544:
3542:
3539:
3535:
3532:
3530:
3527:
3525:
3522:
3521:
3519:
3517:
3514:
3512:
3509:
3508:
3506:
3502:
3495:
3492:
3489:
3486:
3483:
3480:
3477:
3473:
3470:
3467:
3463:
3460:
3458:
3455:
3454:
3452:
3450:
3446:
3440:
3437:
3435:
3434:Cardiac index
3432:
3430:
3427:
3425:
3422:
3419:
3416:
3414:
3410:
3407:
3406:
3404:
3402:
3398:
3392:
3389:
3387:
3384:
3382:
3379:
3377:
3374:
3372:
3369:
3367:
3364:
3362:
3359:
3355:
3352:
3350:
3347:
3346:
3345:
3344:Stroke volume
3342:
3338:
3337:Stroke volume
3335:
3333:
3330:
3329:
3328:
3325:
3323:
3322:Cardiac cycle
3320:
3319:
3317:
3315:
3311:
3308:
3306:
3302:
3298:
3291:
3286:
3284:
3279:
3277:
3272:
3271:
3268:
3261:
3258:
3255:
3252:
3251:
3240:
3238:9780781768528
3234:
3230:
3226:
3221:
3217:
3215:9780878936977
3211:
3207:
3202:
3198:
3196:9781111577438
3192:
3188:
3184:
3179:
3175:
3173:9780495391845
3169:
3165:
3161:
3156:
3152:
3148:
3144:
3140:
3136:
3132:
3128:
3124:
3120:
3116:
3111:
3110:
3097:
3093:
3089:
3085:
3081:
3077:
3073:
3069:
3062:
3054:
3050:
3046:
3042:
3038:
3034:
3030:
3026:
3022:
3018:
3011:
3003:
2999:
2995:
2991:
2987:
2983:
2979:
2975:
2971:
2967:
2963:
2959:
2952:
2944:
2940:
2935:
2930:
2926:
2922:
2918:
2914:
2910:
2903:
2895:
2891:
2886:
2881:
2878:(3): 269–77.
2877:
2873:
2872:
2867:
2860:
2852:
2848:
2844:
2840:
2836:
2832:
2825:
2817:
2813:
2809:
2805:
2800:
2795:
2791:
2787:
2783:
2776:
2768:
2764:
2760:
2756:
2751:
2746:
2742:
2738:
2734:
2727:
2719:
2715:
2711:
2707:
2703:
2699:
2695:
2691:
2684:
2676:
2672:
2668:
2664:
2660:
2656:
2652:
2648:
2644:
2640:
2632:
2625:
2624:Sherwood 2012
2620:
2603:
2596:
2588:
2587:
2579:
2571:
2567:
2563:
2559:
2555:
2551:
2547:
2543:
2539:
2535:
2527:
2519:
2513:
2506:
2505:Sherwood 2008
2501:
2493:
2489:
2485:
2481:
2477:
2473:
2469:
2465:
2458:
2450:
2446:
2441:
2436:
2432:
2428:
2424:
2420:
2416:
2412:
2408:
2401:
2393:
2387:
2383:
2376:
2369:
2368:Sherwood 2008
2364:
2356:
2350:
2346:
2341:
2340:
2334:
2328:
2322:, p. 49.
2321:
2316:
2308:
2304:
2300:
2296:
2292:
2288:
2281:
2273:
2269:
2265:
2261:
2257:
2253:
2250:(4): 509–26.
2249:
2245:
2244:Pharmacol Rev
2238:
2230:
2226:
2221:
2216:
2212:
2208:
2204:
2197:
2190:
2189:Sherwood 2012
2185:
2177:
2171:
2163:
2159:
2155:
2153:9781437717532
2149:
2145:
2138:
2132:, p. 45.
2131:
2126:
2119:
2114:
2106:
2102:
2097:
2092:
2088:
2084:
2080:
2076:
2072:
2065:
2057:
2053:
2048:
2043:
2039:
2035:
2031:
2027:
2023:
2016:
2008:
2004:
2000:
1996:
1991:
1986:
1982:
1978:
1974:
1967:
1965:
1956:
1952:
1947:
1942:
1938:
1934:
1930:
1923:
1915:
1911:
1907:
1903:
1899:
1895:
1888:
1879:
1877:
1875:
1873:
1858:
1854:
1847:
1839:
1835:
1830:
1825:
1821:
1817:
1813:
1809:
1805:
1798:
1790:
1784:
1780:
1776:
1772:
1765:
1757:
1753:
1748:
1743:
1738:
1733:
1729:
1725:
1721:
1717:
1713:
1706:
1698:
1694:
1689:
1684:
1680:
1676:
1672:
1668:
1664:
1657:
1655:
1646:
1644:9781461437840
1640:
1636:
1635:
1627:
1619:
1615:
1610:
1605:
1601:
1597:
1593:
1589:
1585:
1578:
1570:
1566:
1561:
1556:
1551:
1546:
1542:
1538:
1534:
1527:
1519:
1515:
1510:
1505:
1500:
1495:
1491:
1487:
1483:
1476:
1468:
1464:
1460:
1456:
1452:
1448:
1444:
1440:
1433:
1429:
1422:
1420:
1416:
1412:
1411:beta blockers
1408:
1404:
1403:heart rhythms
1400:
1393:
1388:
1384:
1375:
1369:
1361:
1357:
1353:
1349:
1345:
1341:
1337:
1332:
1330:
1326:
1318:
1314:
1313:noradrenaline
1310:
1306:
1302:
1298:
1293:
1291:
1281:
1279:
1275:
1270:
1266:
1264:
1260:
1259:bundle of His
1256:
1252:
1248:
1244:
1240:
1236:
1232:
1225:
1220:
1211:
1207:
1205:
1201:
1197:
1193:
1189:
1185:
1175:
1170:
1163:
1156:
1150:
1145:
1138:
1134:
1130:
1121:
1116:
1110:
1097:
1089:
1085:
1081:
1071:
1068:
1062:
1052:
1045:
1040:
1030:
1028:
1023:
1021:
1017:
1013:
1009:
1005:
1001:
997:
986:
984:
981:
979:
976:
971:
968:
965:
964:
960:
958:
955:
953:
952:3Na-2K-ATPase
950:
945:
942:
939:
938:
934:
931:
927:
924:
922:
919:
914:
911:
908:
907:
903:
901:
897:
893:
890:
888:
881:
876:
873:
870:
869:
865:
863:
860:
857:
849:
844:
841:
838:
837:
833:
831:
828:
821:
816:
813:
810:
809:
805:
803:
799:
796:
789:
784:
781:
778:
777:
773:
771:
768:
761:
756:
753:
750:
749:
745:
743:
740:
733:
728:
725:
722:
721:
718:Phase / role
708:
701:
695:
685:
682:
677:
673:
672:cardiac cells
670:neighbouring
669:
665:
664:Gap junctions
659:Gap junctions
656:
654:
650:
646:
642:
637:
635:
625:
618:
615:
611:
606:
596:
589:K channels (I
588:
584:
580:
572:
568:
558:
555:
548:
542:
538:
528:
525:
513:
511:
507:
502:
495:
492:(Ca) through
491:
487:
483:
479:
478:gap junctions
471:
466:
464:
460:
450:
448:
443:
439:
434:
433:(see below).
432:
431:funny current
428:
423:
421:
417:
412:
410:
406:
400:
398:
394:
390:
386:
385:potassium (K)
382:
377:
373:
370:
365:
362:
358:
343:
339:
332:
327:
318:
316:
312:
308:
304:
301:
297:
293:
284:
282:
278:
274:
270:
265:
263:
259:
255:
251:
247:
243:
239:
235:
231:
226:
223:
219:
209:
204:
200:
197:
194:
191:
188:
187:
183:
180:
177:
174:
171:
170:
166:
163:
160:
157:
154:
153:
149:
146:
143:
140:
137:
136:
119:
116:
114:
110:
106:
94:
92:
88:
84:
80:
71:
67:
65:
61:
58:in the right
57:
53:
49:
45:
41:
32:
19:
3848:Carotid body
3811:Vasodilators
3691:hemodynamics
3523:
3496:(Relaxation)
3488:Bathmotropic
3462:Chronotropic
3224:
3206:Neuroscience
3205:
3182:
3159:
3118:
3114:
3106:Bibliography
3071:
3067:
3061:
3020:
3016:
3010:
2961:
2957:
2951:
2916:
2912:
2902:
2875:
2869:
2859:
2834:
2830:
2824:
2789:
2785:
2775:
2740:
2736:
2726:
2693:
2690:Heart Rhythm
2689:
2683:
2642:
2638:
2631:
2619:
2608:. Retrieved
2595:
2586:Neuroscience
2585:
2578:
2537:
2533:
2526:
2512:
2500:
2467:
2463:
2457:
2414:
2410:
2400:
2381:
2375:
2363:
2338:
2327:
2315:
2290:
2286:
2280:
2247:
2243:
2237:
2210:
2206:
2196:
2184:
2143:
2137:
2125:
2113:
2081:(1): 30–41.
2078:
2074:
2064:
2032:(2): 211–9.
2029:
2025:
2015:
1980:
1976:
1936:
1932:
1922:
1897:
1893:
1887:
1860:. Retrieved
1856:
1846:
1814:(1): 23–45.
1811:
1807:
1797:
1770:
1764:
1719:
1715:
1705:
1670:
1666:
1633:
1626:
1594:(2): 53–64.
1591:
1587:
1577:
1540:
1536:
1526:
1489:
1485:
1475:
1442:
1438:
1432:
1397:
1333:
1329:cAMP pathway
1294:
1287:
1271:
1267:
1228:
1208:
1181:
1168:
1161:
1154:
1151:
1143:
1136:
1128:
1117:
1108:
1086:
1083:
1064:
1042:
1033:HCN channels
1024:
992:
982:
969:
956:
943:
925:
912:
874:
842:
814:
782:
754:
726:
706:
693:
667:
662:
647:. The rapid
638:
631:
619:
607:
597:K current, I
564:
556:
549:
534:
526:
519:
503:
490:calcium ions
467:
456:
435:
424:
413:
401:
378:
374:
366:
354:
336:
303:muscle cells
295:
291:
290:
281:ion channels
266:
250:calcium (Ca)
227:
215:
207:
102:
76:
37:
3853:Glomus cell
3843:Aortic body
3838:Paraganglia
3649:ventricular
3622:ventricular
3571:QT interval
3566:QRS complex
3561:PR interval
3534:ventricular
3472:Dromotropic
2333:Bullock, TH
1348:vagus nerve
1344:chronotropy
1309:spinal cord
1305:chronotropy
1039:HCN channel
994:a specific
887:2.1/2.2/2.3
567:Ca channels
470:Na channels
381:sodium (Na)
307:ion channel
236:that allow
38:Unlike the
3874:Categories
3791:Baroreflex
3708:Compliance
3700:Blood flow
3576:ST segment
3504:Conduction
3494:Lusitropic
3466:Heart rate
3449:Heart rate
3401:Ultrasound
3332:Heart rate
2610:2013-03-14
1862:2022-05-17
1425:References
1255:ventricles
593:) and the
579:K channels
300:conductive
91:ventricles
3751:Diastolic
3723:Perfusion
3482:Inotropic
3361:Afterload
3088:0363-6135
3037:0031-6768
2986:0028-0836
2843:0014-9446
2808:0009-7330
2759:0008-6363
2710:1547-5271
2659:1522-1210
2484:1071-9164
2431:1943-0264
2170:cite book
2162:756281854
2087:0730-2347
1999:1524-4571
806:1, notch
705:Current (
694:Figure 3:
414:However,
346:current).
201:2 x 10:1
161:3.5 - 5.0
155:Potassium
144:135 - 145
3746:Systolic
3524:cardiac
3151:13231624
3143:18375583
3096:10362707
3053:32845421
2943:14617564
2816:10746994
2767:10533574
2718:15851327
2667:20086079
2492:12555135
2449:20066080
2307:14693686
2272:11588492
2264:16382105
2229:20132149
2213:: 1–48.
2056:21319337
2007:20167941
1955:20132149
1939:: 1–48.
1851:Krul S.
1838:21892379
1756:21298076
1697:20850450
1618:16863387
1569:25113792
1518:24578694
1467:52919432
1459:30288656
1368:-protein
1352:molecule
1243:Purkinje
1196:T-tubule
1147:to, slow
996:molecule
688:Channels
681:connexon
612:and the
357:diastole
189:Calcium
178:95 - 110
172:Chloride
121:Element
97:Overview
3366:Preload
3123:Bibcode
3045:6253873
3002:4326191
2994:1709448
2966:Bibcode
2934:1767992
2570:4246540
2562:1650913
2542:Bibcode
2440:2742079
2105:7514060
2047:3051220
1914:6277179
1829:3164530
1747:3029229
1724:Bibcode
1688:3623268
1609:1614214
1560:4149194
1543:: 122.
1509:3936571
1354:called
1229:In the
1140:to,fast
794:4.2/4.3
770:CACNA1C
561:Phase 3
531:Phase 2
516:Phase 1
453:Phase 0
351:Phase 4
271:of the
181:10 - 20
3656:Aortic
3644:atrial
3617:atrial
3613:Right
3586:U wave
3581:T wave
3556:P wave
3529:atrial
3235:
3212:
3193:
3170:
3149:
3141:
3094:
3086:
3051:
3043:
3035:
3000:
2992:
2984:
2958:Nature
2941:
2931:
2894:330018
2892:
2851:350631
2849:
2841:
2814:
2806:
2765:
2757:
2716:
2708:
2675:472259
2673:
2665:
2657:
2568:
2560:
2534:Nature
2490:
2482:
2447:
2437:
2429:
2388:
2351:
2305:
2270:
2262:
2227:
2160:
2150:
2103:
2096:325129
2093:
2085:
2054:
2044:
2005:
1997:
1953:
1912:
1836:
1826:
1785:
1754:
1744:
1695:
1685:
1641:
1616:
1606:
1567:
1557:
1516:
1506:
1492:: 82.
1465:
1457:
1417:, and
1340:nerves
1200:atrial
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