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Cardiac pacemaker
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==Generation of action potentials== There are three main stages in the generation of an action potential in a pacemaker cell. Since the stages are analogous to contraction of '''cardiac muscle cells''', they have the same naming system. This can lead to some confusion as phases one and two are absent, leaving only phases zero, three, and four. ===Phase 4{{Dash}}Pacemaker potential=== The key to the rhythmic firing of pacemaker cells is that, unlike [[neuron]]s, these cardiomyocytes will slowly depolarize by themselves and do not need any outside innervation from the autonomic nervous system to fire action potentials. In all other cells, the [[resting potential]] (-60mV to -70mV) is caused by a continuous outflow or "leak" of [[potassium]] ions through [[ion channel]] [[integral membrane protein|proteins]] in the [[cell membrane|membrane]] that surrounds the cells. However, in pacemaker cells, this potassium permeability (efflux) decreases as time goes on, causing a slow depolarization. In addition, there is a slow, continuous inward flow of [[sodium]], called the funny current, or [[pacemaker current]]. These two relative ion concentration changes slowly depolarize (make more positive) the inside membrane potential (voltage) of the cell, giving these cells their pacemaker potential. When the membrane potential gets depolarized to about -40mV it has reached threshold (cells enter phase 0), allowing an action potential to be generated. === Phase 0{{Dash}}Upstroke === Though much faster than the depolarization of phase 4, the upstroke in a pacemaker cell is slow compared to that in an [[axon]]. The SA and AV node do not have fast sodium channels like neurons, and the depolarization is mainly caused by a slow influx of calcium ions. (The funny current also increases). Calcium enters the cell via voltage-sensitive calcium channels that open when the threshold is reached. This calcium influx produces the rising phase of the action potential, which results in the reversal of membrane potential to a peak of about +10mV. It is important to note that intracellular calcium causes muscular contraction in contractile cells, and is the effector ion. In heart pacemaker cells, phase 0 depends on the activation of [[L-type calcium channel]]s instead of the activation of voltage-gated fast sodium channels, which are responsible for initiating action potentials in contractile (non-pacemaker) cells. For this reason, the pacemaker action potential rising phase slope is more gradual than that of the contractile cell (image 2). === Phase 3{{Dash}}Repolarization === The reversal of membrane potential triggers the opening of potassium leak channels, resulting in the rapid loss of potassium ions from the inside of the cell, causing repolarization (V<sub>m</sub> gets more negative). The calcium channels are also inactivated soon after they open. In addition, as sodium channels become inactivated, sodium permeability into the cell is decreased. These ion concentration changes slowly repolarize the cell to resting membrane potential (-60mV). Another important note at this phase is that ionic pumps restore ion concentrations to pre-action potential status. The [[sodium-calcium exchanger]] ionic pump works to pump calcium out of the [[intracellular space]], thus effectively relaxing the cell. The [[sodium/potassium pump]] restores ion concentrations of sodium and potassium ions by pumping sodium out of the cell and pumping (exchanging) potassium into the cell. Restoring these ion concentrations is vital because it enables the cell to reset itself and enables it to repeat the process of spontaneous depolarization leading to activation of an action potential.
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