Download Non-Pacemaker Action Potentials

Non-Pacemaker Action Potentials
Atrial myocytes, ventricular myocytes and Purkinje cells are examples of non-pacemaker action
potentials in the heart. Because these action potentials undergo very rapid depolarization, they
are sometimes referred to as "fast response" action potentials.
Unlike pacemaker cells found in nodal tissue within the heart, non-pacemaker cells have a true
resting membrane potential (phase 4) that remains near the equilibrium potential for K+ (EK). The
resting membrane potential is very negative during phase 4 (about -90 mV) because potassium
channels are open (K+ conductance [gK+] and K+ currents [IK] are high). As shown in the figure,
phase 4 is associated with K+ currents, in which positive potassium ions are leaving the cell and
thereby making the membrane potential more negative inside. At the same time, fast sodium
channels and (L-type) slow calcium channels are closed.
When these cells are rapidly depolarized to a threshold voltage of about -70 mV (e.g., by an
action potential in an adjacent cell), there is a rapid depolarization (phase 0) that is caused by a
transient increase in fast Na+-channel conductance (gNa+) through fastsodium channels. This
increases the inward directed, depolarizing Na+ currents (INa) that are responsible for the
generation of these "fast-response" action potentials (see above figure). At the same time sodium
channels open, gK+ and outward directed K+ currents fall as potassium channels close. These
two conductance changes move the membrane potential away from EK (which is negative) and
closer toward the equilibrium potential for sodium (ENa), which is positive.
Phase 1 represents an initial repolarization that is caused by the opening of a special type of
transient outward K+ channel (Kto), which causes a short-lived, hyperpolarizing outward K+ current
(IKto). However, because of the large increase in slow inward gCa++ occurring at the same time
and the transient nature of IKto, the repolarization is delayed and there is a plateau phase in the
action potential (phase 2). This inward calcium movement is through long-lasting (L-type) calcium
channels that open up when the membrane potential depolarizes to about -40 mV. This plateau
phase prolongs the action potential duration and distinguishes cardiac action potentials from the
much shorter action potentials found in nerves and skeletal muscle.
These fast-response action potentials in non-nodal tissue are altered by antiarrhythmic drugs that
block specific ion channels. Sodium-channel blockers such as quinidine inactivate fast-sodium
channels and reduce the rate of depolarization (decrease the slope of phase 0). Calcium-channel
blockers such as verapamil and diltiazem affect the plateau phase (phase 2) of
the action potential. Potassium-channel blockers delay repolarization (phase 3) by
blocking the potassium channels that are responsible for this phase.
Effective Refractory Period
Once an action potential is initiated, there is a period of time comprising phases 0, 1, 2, and part
of phase 3 that a new action potential cannot be initiated. This is termed the effective refractory
period (ERP) or the absolute refractory period (ARP) of the cell. During the ERP, stimulation of
the cell by an adjacent cell undergoing depolarization does not produce new, propagated action
potentials. The ERP acts as a protective mechanism in the heart by preventing multiple,
compounded action potentials from occurring (i.e., it limits the frequency of depolarization and
therefore heart rate). This is important because at very high heart rates, the heart would be
unable to adequately fill with blood and therefore ventricular ejection would be reduced.
Many antiarrhythmic drugs alter the ERP, thereby altering cellular excitability. For
example, drugs that block potassium channels (e.g., amiodarone, a Class III antiarrhythmic)
delays phase 3 repolarization and increases the ERP. Drugs that increase the ERP can be
particularly effective in abolishing reentry currents that lead to tachyarrhythmias.
Transformation of non-pacemaker into pacemaker cells
It is important to note that non-pacemaker action potentials can change into pacemaker cells
under certain conditions. For example, if a cell becomes hypoxic, the membrane depolarizes,
which closes fast Na+ channels. At a membrane potential of about –50 mV, all the fast
Na+ channels are inactivated. When this occurs, action potentials can still be elicited; however,
the inward current are carried by Ca++ (slow inward channels) exclusively. These action potentials
resemble those found in pacemaker cells located in the SA node,and can sometimes display
spontaneous depolarization and automaticity. This mechanism may serve as the
electrophysiological mechanism behind certain types of ectopic beats and arrhythmias,
particularly in ischemic heart disease and following myocardial infarction.