Editing Pacemaker potential (section)

== Background ==
{{See also|Cardiac pacemaker}}
The '''cardiac pacemaker''' is the [[heart]]'s natural rhythm generator. It employs pacemaker [[Cell (biology)|cells]] that generate electrical impulses, known as [[Cardiac action potential|cardiac action potentials]]. These potentials cause the [[cardiac muscle]] to contract, and the rate of which these muscles contract determines the [[heart rate]].

As with any other cells, pacemaker cells have an electrical charge on their membranes. This electrical charge is called the [[membrane potential]]. After the firing of an action potential, the pacemaking cell's membrane [[Repolarization|repolarizes]] (decreases in voltage) to its [[resting potential]] of -60 mV. From here, the membrane gradually [[Depolarization|depolarizes]] (increases in voltage) to the [[threshold potential]] of -40 mV,<ref>{{cite book |last1=Wei |first1=Xingyu |title=StatPearls |last2=Yohannan |first2=Sandesh |last3=Richards |first3=John R. |date=2025 |publisher=StatPearls Publishing |chapter=Physiology, Cardiac Repolarization Dispersion and Reserve |pmid=30725879 |quote=[Depolarization] starts when the membrane potential reaches -40 mV, the threshold potential for pacemaker cells. [...This] results in an upstroke in membrane potential from -40 mV to +10mV. [... Repolarization involves a] rapid decrease of membrane potential from +10 mV to -60 mV. |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK537194/}}</ref> upon which the cell would go on to fire the next action potential. The rate of depolarization is the slope: the faster voltage increases, the steeper the slopes are in graphs. The slope determines the time taken to reach the threshold potential, and thus the timing of the next action potential.<ref>{{cite book |last1=Sokolov |first1=E.N. |title=Brain and Behaviour |last2=Grechenko |first2=T.N. |date=1981 |isbn=978-0-08-027338-9 |pages=7–12 |chapter=Pacemaker Plasticity in Isolated Neuron |doi=10.1016/B978-0-08-027338-9.50007-4 |quote=[When the pacemaker potential] reaches threshold (approximately –40mV in nodal cells) it triggers an action potential, which sparks off the next heart beat. The slope of the pacemaker potential determines the time taken to reach the threshold value, so the slope governs heart rate; the steeper the slope the sooner threshold is reached and the shorter the time between beats. Since the pacemaker slope is steeper in SA node cells than elsewhere in the electrical system, the SA node has the fastest intrinsic firing rate and initiates each heart beat.}}</ref>

In a healthy sinoatrial node (SAN, a complex tissue within the right atrium containing pacemaker cells that normally determine the intrinsic firing rate for the entire heart<ref name="pmid17823213">{{cite journal |vauthors=Verkerk AO, van Boren MM, Peters RJ, Broekhuis E, Lam K, Coronel R, de Bakker JM, Tan HR |title=Pacemaker current (I<sub>f</sub>) in the human sinoatrial node |journal=European Heart Journal |date=7 September 2007 |volume=28 |issue=20 |pages=2472–2478 |pmid=17823213 |doi=10.1093/eurheartj/ehm339 |doi-access=free }}</ref><ref>{{cite book
  | last = Boron
  | first = Walter. F
  |author2=Emile Boulpaep
  | title = Medical Physiology
  | publisher = Elsevier Saunders
  | year = 2003
  | page = 489
  | isbn = 978-0-7216-0076-5
  }}</ref>), the pacemaker potential is the main determinant of the heart rate. Because the pacemaker potential represents the non-contracting time between heart beats ([[diastole]]), it is also called the '''[[diastolic depolarization]]'''.
The amount of net inward current required to move the cell membrane potential during the pacemaker phase is extremely small, in the order of few pAs, but this net flux arises from time to time changing contribution of several currents that flow with different voltage and time dependence. Evidence in support of the active presence of K<sup>+</sup>, Ca<sup>2+</sup>, Na<sup>+</sup> channels and Na<sup>+</sup>/K<sup>+</sup> exchanger during the pacemaker phase have been variously reported in the literature, but several indications point to the “funny”(I<sub>f</sub>) current as one of the most important.<ref>{{cite journal |author=DiFrancesco D |title=Funny channels in the control of cardiac rhythm and mode of action of selective blockers |journal=Pharmacol. Res. |volume=53 |issue=5 |pages=399–406 |date=May 2006 |pmid=16638640 |doi=10.1016/j.phrs.2006.03.006 }}</ref> (see [[funny current]]). There is now substantial evidence that also sarcoplasmic reticulum (SR) Ca<sup>2+</sup>-transients participate to the generation of the diastolic depolarization via a process involving the Na–Ca exchanger.

The rhythmic activity of some [[neurons]] like the [[pre-Bötzinger complex]] is modulated by neurotransmitters and neuropeptides, and such modulatory connectivity gives to the neurons the necessary plasticity to generating distinctive, state-dependent rhythmic patterns that depend on pacemaker potentials.<ref>{{Cite book|last1=Morgado-Valle|first1=Consuelo|last2=Beltran-Parrazal|first2=Luis|title=The Plastic Brain |chapter=Respiratory Rhythm Generation: The Whole is Greater Than the Sum of the Parts |series=Advances in Experimental Medicine and Biology |date=2017|volume=1015|pages=147–161|doi=10.1007/978-3-319-62817-2_9|issn=0065-2598|pmid=29080026|isbn=978-3-319-62815-8}}</ref>