Editing Cardiac action potential (section)

==Conduction system==
[[File:Conductionsystemoftheheart.png|thumb|The [[electrical conduction system of the heart]]]]
In the [[electrical conduction system of the heart|heart's conduction system]] electrical activity that originates from the [[sinoatrial node]] (SAN) is propagated via the [[Bundle of His|His]]-[[Purkinje fibers|Purkinje]] network, the fastest conduction pathway within the heart. The electrical signal travels from the sinoatrial node, which stimulates the [[Atrium (heart)|atria]] to contract, to the [[Atrioventricular node|atrioventricular node (AVN)]], which slows down conduction of the action potential from the atria to the [[Ventricle (heart)|ventricles]]. This delay allows the ventricles to fully fill with blood before contraction. The signal then passes down through a bundle of fibres called the [[bundle of His]], located between the ventricles, and then to the [[Purkinje fibers]] at the bottom (apex) of the heart, causing ventricular contraction.{{cn|date=April 2024}}

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 or Purkinje fibres reach the threshold potential for an action potential, they are depolarized by the oncoming impulse from the SAN<ref>{{Cite journal |last=Tsien |first=R. W. |last2=Carpenter |first2=D. O. |date=1978-06-01 |title=Ionic mechanisms of pacemaker activity in cardiac Purkinje fibers |journal=Federation Proceedings |volume=37 |issue=8 |pages=2127–2131 |issn=0014-9446 |pmid=350631}}</ref> This is called "overdrive suppression".<ref name="Vassalle1977">{{Cite journal |last=Vassalle |first=M. |year=1977 |title=The relationship among cardiac pacemakers: Overdrive suppression |journal=[[Circulation Research]] |volume=41 |issue=3 |pages=269–77 |doi=10.1161/01.res.41.3.269 |pmid=330018 |doi-access=free}}</ref> 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.{{cn|date=April 2024}}

An example of premature ventricular contraction is the classic [[athletic heart syndrome]]. 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 [[atrioventricular block]], 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.<ref>{{Cite journal |last=Fagard R |date=2003-12-01 |title=Athlete's heart |journal=Heart |language=en |volume=89 |issue=12 |pages=1455–61 |doi=10.1136/heart.89.12.1455 |pmc=1767992 |pmid=14617564}}</ref>

===Regulation by the autonomic nervous system===
The speed of action potential production in pacemaker cells is affected, but not controlled by the [[autonomic nervous system]].

The [[sympathetic nervous system]] (nerves dominant during the body's [[fight-or-flight response]]) increase heart rate (positive [[Chronotropic|chronotropy]]), by decreasing the time to produce an action potential in the SAN. Nerves from the [[spinal cord]] release a molecule called [[Norepinephrine|noradrenaline]], which binds to and activates receptors on the pacemaker cell membrane called [[Beta-1 adrenergic receptor|β1 adrenoceptors]]. This activates a protein, called a G<sub>s</sub>-protein (s for stimulatory). Activation of this G-protein leads to increased levels of [[Cyclic adenosine monophosphate|cAMP]] in the cell (via the [[CAMP-dependent pathway|cAMP pathway]]). 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<sup>2+</sup> current through the channel, speeding up phase 0.<ref>{{Cite journal |last=DiFrancesco |first=D. |last2=Tortora |first2=P. |date=1991-05-09 |title=Direct activation of cardiac pacemaker channels by intracellular cyclic AMP |journal=Nature |volume=351 |issue=6322 |pages=145–147 |bibcode=1991Natur.351..145D |doi=10.1038/351145a0 |issn=0028-0836 |pmid=1709448 |s2cid=4326191}}</ref>

The [[parasympathetic nervous system]] ([[nerve]]s dominant while the body is resting and digesting) decreases heart rate (negative [[Chronotropic|chronotropy]]), by increasing the time taken to produce an action potential in the SAN. A nerve called the [[vagus nerve]], that begins in the brain and travels to the sinoatrial node, releases a [[molecule]] called [[Acetylcholine|acetylcholine (ACh)]] which binds to a receptor located on the outside of the pacemaker cell, called an [[Muscarinic acetylcholine receptor M2|M2 muscarinic receptor]]. This activates a [[G protein|G<sub>i</sub>-protein]] (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.<ref>{{Cite journal |last=Osterrieder |first=W. |last2=Noma |first2=A. |last3=Trautwein |first3=W. |date=1980-07-01 |title=On the kinetics of the potassium channel activated by acetylcholine in the S-A node of the rabbit heart |journal=Pflügers Archiv: European Journal of Physiology |volume=386 |issue=2 |pages=101–109 |doi=10.1007/bf00584196 |issn=0031-6768 |pmid=6253873 |s2cid=32845421}}</ref> The G<sub>i</sub>-protein also inhibits the cAMP pathway therefore reducing the sympathetic effects caused by the spinal nerves.<ref>{{Cite journal |last=Demir |first=Semahat S. |last2=Clark |first2=John W. |last3=Giles |first3=Wayne R. |date=1999-06-01 |title=Parasympathetic modulation of sinoatrial node pacemaker activity in rabbit heart: a unifying model |journal=American Journal of Physiology. Heart and Circulatory Physiology |language=en |volume=276 |issue=6 |pages=H2221–H2244 |doi=10.1152/ajpheart.1999.276.6.H2221 |issn=0363-6135 |pmid=10362707}}</ref>