Editing Cardiac action potential (section)

===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>