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In the pacemaking cells of the heart , the pacemaker potential is the slow, positive increase in voltage across the cell's membrane that occurs between the end of one action potential and the beginning of the next action potential. This increase in membrane potential is what causes the cell membrane, which typically maintains a resting membrane potential of -70 mV, to reach the threshold potential and consequently fire the next action potential; thus, the pacemaker potential is what drives the self-generated rhythmic firing of pacemaker cells, and the rate of change of the pacemaker potential is what determines the timing of the next action potential and thus the intrinsic firing rate of the cell. In a healthy sinoatrial node , the pacemaker potential is the main determinant of the heart rate. Because the pacemaker potential represents the non-contracting time between heart beats , 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, Ca, Na channels and Na/K exchanger during the pacemaker phase have been variously reported in the literature, but several indications point to the “funny” current as one of the most important.. There is now substantial evidence that also sarcoplasmic reticulum Ca-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.