Editing Pacemaker potential

[[File:Pacemaker potential.svg|thumb|300px]]
In the [[Pacemaker cells|pacemaking cells]] of the [[heart]] (e.g., the [[sinoatrial node]]), the '''pacemaker potential''' (also called the '''pacemaker current''') is the slow, positive increase in voltage across the [[cardiac myocyte|cell]]'s membrane, that occurs between the end of one [[action potential]] and the beginning of the next. It is responsible for the self-generated rhythmic firing ([[Cardiac automaticity|automaticity]]) of pacemaker cells.

== 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>

==Pacemakers==
[[File:Pacemaker rates.svg|thumb|Pacemaker rates]]
The heart has several pacemakers, each which fires at its own intrinsic rate:
* ''SA node:'' 60–100 bpm
* ''Atrioventricular node(AVN):'' 40–60 bpm
* ''Purkinje fibres:'' 20–40 bpm

The potentials will normally travel in order<br/>
SA node → Atrioventricular node → Purkinje fibres

Normally, all the foci will end up firing at the SA node rate, not their intrinsic rate in a phenomenon known as overdrive-suppression. Thus, in the normal, healthy heart, only the SA node intrinsic rate is observable.

==Pathology==
However, in pathological conditions, the intrinsic rate becomes apparent. Consider a heart attack which damages the region of the heart between the SA node and the AV node.

SA node → |block| AV node → Purkinje fibres 

The other foci will not see the SA node firing; however, they will see the atrial foci. The heart will now beat at the intrinsic rate of the AV node.

==Induction==
The firing of the pacemaker cells is induced electrically by reaching the threshold potential of the cell membrane. The [[threshold potential]] is the potential an excitable cell membrane, such as a [[myocyte]], must reach in order to induce an action potential.<ref>{{cite book
  | last = Campbell
  | first = Neil. A
  | title = Biology
  | url = https://archive.org/details/biologycamp00camp
  | url-access = registration
  | publisher = Benjamin Cummings
  | year = 1996
  | page = G–21
  | isbn = 978-0-07-366175-9
}}</ref> This [[depolarization]] is caused by very small net inward currents of calcium ions across the cell membrane, which gives rise to the action potential.<ref name="pmid19181406">{{cite journal |last1=Verkerk |first1=Arie O. |last2=van Ginneken |first2=Antoni C.G. |last3=Wilders |first3=Ronald |title=Pacemaker activity of the human sinoatrial node: Role of the hyperpolarization-activated current, If |journal=International Journal of Cardiology |date=March 2009 |volume=132 |issue=3 |pages=318–336 |doi=10.1016/j.ijcard.2008.12.196 |pmid=19181406 }}</ref><ref>{{cite book
  | last = Boron
  | first = Walter. F
  |author2=Emile Boulpaep
  | title = Medical Physiology
  | publisher = Elsevier Saunders
  | year = 2003
  | page = 487
  | isbn = 978-0-7216-0076-5
}}</ref>

==Bio-pacemakers==
Bio-pacemakers are the outcome of a rapidly emerging field of research into a replacement for the [[electronic pacemaker]]. The bio-pacemaker turns quiescent myocardial cells (e.g. atrial cells) into pacemaker cells. This is achieved by making the cells express a gene which creates a pacemaker current.<ref name="pmid19162611">{{cite book |vauthors=Verkerk AO, Zegers JG, Van Ginneken AC, Wilders R |title=2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society |chapter=Dynamic action potential clamp as a powerful tool in the development of a gene-based bio-pacemaker |date=2008 |volume=1 |pages=133–6 |pmid=19162611 |doi=10.1109/IEMBS.2008.4649108 |isbn=978-1-4244-1814-5 }}</ref>

==See also==
* [[Pacemaker action potential]]
* [[Graded potential]]

==References==
{{reflist}}

{{Cardiovascular physiology}}

{{DEFAULTSORT:Pacemaker Potential}}
[[Category:Cardiac electrophysiology]]
[[Category:Graded potentials]]