Editing Cardiac action potential (section)

==Channels==

{| class="wikitable" align="center"
|+ '''Figure 3:''' Major currents during the cardiac ventricular action potential<small>{{sfn|Sherwood|2008|pp=248-50}}</small>
|---
! width="60" style="background:#efefef;" |
! width="30" style="background:#efefef;" | Current (''I'')
! width="50" style="background:#efefef;" | α subunit protein
! width="60" style="background:#efefef;" | α subunit gene
! width="50" style="background:#efefef;" | Phase / role
|---
| Na<sup>+</sup> || ''I''<sub>Na</sub> || Na<sub>V</sub>1.5 || [[SCN5A]]<ref>{{Cite web |title=SCN5A sodium channel, voltage-gated, type V, alpha subunit [Homo sapiens (human)] |url=https://www.ncbi.nlm.nih.gov/gene/6331 |publisher=National Center for Biotechnology Information}}</ref>|| 0
|---
| Ca<sup>2+</sup> || ''I''<sub>Ca(L)</sub> || Ca<sub>V</sub>1.2 || [[CACNA1C]]<ref name="pmid1650913">{{Cite journal |last=Lacerda |first=AE |last2=Kim |first2=HS |last3=Ruth |first3=P |last4=Perez-Reyes |first4=E |last5=Flockerzi |first5=V |last6=Hofmann |first6=F |last7=Birnbaumer |first7=L |last8=Brown |first8=AM |display-authors=4 |date=August 1991 |title=Normalization of current kinetics by interaction between the alpha 1 and beta subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel |journal=Nature |volume=352 |issue=6335 |pages=527–30 |bibcode=1991Natur.352..527L |doi=10.1038/352527a0 |pmid=1650913 |s2cid=4246540}}</ref> || 0-2
|---
| K<sup>+</sup> || ''I''<sub>to1</sub> || K<sub>V</sub>4.2/4.3 || [[KCND2]]/[[KCND3]] || 1, notch
|---
| K<sup>+</sup> || ''I''<sub>Ks</sub> || K<sub>V</sub>7.1 || [[KCNQ1]] || 2,3
|-----
| K<sup>+</sup> || ''I''<sub>Kr</sub> || K<sub>V</sub>11.1 ([[hERG]]) || [[KCNH2]] || 3
|---
| K<sup>+</sup> || ''I''<sub>K1</sub> || [[Inward-rectifier potassium ion channel|K<sub>ir</sub>2.1/2.2/2.3]] || [[KCNJ2]]/[[KCNJ12]]/[[KCNJ4]] || 3,4
|---
| Na<sup>+</sup>, Ca<sup>2+</sup> || ''I''<sub>NaCa</sub> || [[Sodium-calcium exchanger|3Na<sup>+</sup>-1Ca<sup>2+</sup>-exchanger]] || ''NCX1'' ([[SLC8A1]]) || ion homeostasis
|---
| Na<sup>+</sup>, K<sup>+</sup> || ''I''<sub>NaK</sub> || [[Na+/K+-ATPase|3Na<sup>+</sup>-2K<sup>+</sup>-ATPase]] || ''ATP1A'' || ion homeostasis
|---
| Ca<sup>2+</sup> || ''I''<sub>pCa</sub> || [[Calcium ATPase|Ca<sup>2+</sup>-transporting ATPase]] || ''ATP1B'' || ion homeostasis
|}
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 a specific [[molecule]] to a receptor on the channel (also known as [[ligand-gated ion channels]]) or a change in membrane potential around the channel, detected by a sensor (also known as [[voltage-gated ion channels]]) 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.<ref>{{Cite book |last=Purves |first=Dale |url=https://www.ncbi.nlm.nih.gov/books/NBK11123/ |title=Neuroscience |last2=Augustine |first2=George J. |last3=Fitzpatrick |first3=David |last4=Katz |first4=Lawrence C. |last5=LaMantia |first5=Anthony-Samuel |last6=McNamara |first6=James O. |last7=Williams |first7=S. Mark |date=2001-01-01 |edition=2nd |language=en |chapter=The Molecular Structure of Ion Channels}}</ref> Ion channels can be selective for specific ions, so there are [[Sodium channels|Na<sup>+</sup>]], [[Potassium channels|K<sup>+</sup>]], [[Calcium channels|Ca<sup>2+</sup>]], and [[Chloride channels|Cl<sup>−</sup>]] specific channels. They can also be specific for a certain charge of ions (i.e. positive or negative).<ref>{{Cite web |last=Sheng |first=Morgan |title=Ion channels and receptors |url=http://web.mit.edu/9.013/www/lectures/01-02_MS_Ion_Channels.pdf |access-date=2013-03-14}}</ref>

Each channel is coded by a set of DNA instructions that tell the cell how to make it. These instructions are known as a [[gene]]. 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.

===HCN channels===
{{Main |HCN channel}}
[[HCN channel|Hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels)]] are located mainly in pacemaker cells, these channels become active at very negative membrane potentials and allow for the passage of both Na<sup>+</sup> and K<sup>+</sup> into the cell (which is a movement known as a funny current, I<sub>f</sub>). 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).{{sfn|Sherwood|2012|pp=310-1}}<ref name="DiFrancesco funny">{{Cite journal |last=DiFrancesco |first=Dario |date=2010-02-19 |title=The role of the funny current in pacemaker activity |journal=Circulation Research |volume=106 |issue=3 |pages=434–446 |doi=10.1161/CIRCRESAHA.109.208041 |issn=1524-4571 |pmid=20167941 |doi-access=free}}</ref>

===The fast sodium channel===
{{main|Sodium channel}}
These [[sodium channel]]s 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 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<sup>+</sup> cannot pass through (absolute refractory period). However they begin to recover from inactivation as the membrane potential becomes more negative (relative refractory period).{{cn|date=May 2025}}

===Potassium channels===
{{main|Potassium channel}}

The two main types of potassium channels in cardiac cells are inward rectifiers and voltage-gated potassium channels.{{cn|date=April 2024}}

[[Inward-rectifier potassium ion channel|Inwardly rectifying potassium channels]] (K<sub>ir)</sub> favour the flow of K<sup>+</sup> into the cell. This influx of potassium, however, is larger when the membrane potential is more negative than the [[Reversal potential|equilibrium potential]] for K<sup>+</sup> (~-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<sub>ir</sub> decreases. Therefore, K<sub>ir</sub> 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<sup>+</sup> ''out'' of the cell. This outward flow of potassium ions at the more positive membrane potentials means that the K<sub>ir</sub> can also aid the final stages of repolarisation.<ref>{{Cite journal |last=Hibino |first=Hiroshi |last2=Inanobe |first2=Atsushi |last3=Furutani |first3=Kazuharu |last4=Murakami |first4=Shingo |last5=Findlay |first5=Ian |last6=Kurachi |first6=Yoshihisa |date=2010-01-01 |title=Inwardly rectifying potassium channels: their structure, function, and physiological roles |journal=Physiological Reviews |volume=90 |issue=1 |pages=291–366 |doi=10.1152/physrev.00021.2009 |issn=1522-1210 |pmid=20086079 |s2cid=472259}}</ref><ref>{{Cite journal |last=Dhamoon |first=Amit S. |last2=Jalife |first2=José |date=2005-03-01 |title=The inward rectifier current (IK1) controls cardiac excitability and is involved in arrhythmogenesis |journal=Heart Rhythm |volume=2 |issue=3 |pages=316–324 |doi=10.1016/j.hrthm.2004.11.012 |issn=1547-5271 |pmid=15851327}}</ref>

The [[voltage-gated potassium channel]]s (K<sub>v</sub>) are activated by depolarization. The currents produced by these channels include the transient out potassium current [[Cardiac transient outward potassium current|''I''<sub>to1</sub>]]. This current has two components. Both components activate rapidly, but ''I''<sub>to,fast</sub> inactivates more rapidly than ''I''<sub>to, slow</sub>. These currents contribute to the early repolarization phase (phase 1) of the action potential.{{cn|date=April 2024}}

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 ''I''<sub>Ks</sub>, rapidly activating ''I''<sub>Kr</sub> and ultra-rapidly activating ''I''<sub>Kur</sub>.<ref>{{Cite journal |last=Snyders |first=D. J. |date=1999-05-01 |title=Structure and function of cardiac potassium channels |journal=Cardiovascular Research |volume=42 |issue=2 |pages=377–390 |doi=10.1016/s0008-6363(99)00071-1 |issn=0008-6363 |pmid=10533574 |doi-access=free}}</ref>

===Calcium channels===
There are two [[Voltage-dependent calcium channel|voltage-gated calcium channels]] within cardiac muscle: [[L-type calcium channel]]s ('L' for Long-lasting) and [[T-type calcium channel]]s ('T' for Transient, i.e. short). L-type channels are more common and are most densely populated within the [[T-tubule]] membrane of ventricular cells, whereas the T-type channels are found mainly within [[Atrium (heart)|atrial]] and [[Cardiac pacemaker|pacemaker cells]], but still to a lesser degree than L-type channels.{{cn|date=April 2024}}

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 L-type channels contribute to the plateau (phase 2).<ref>{{Cite journal |last=Nargeot |first=J. |date=2000-03-31 |title=A tale of two (Calcium) channels |journal=Circulation Research |volume=86 |issue=6 |pages=613–615 |doi=10.1161/01.res.86.6.613 |issn=0009-7330 |pmid=10746994 |doi-access=free}}</ref>