Changes in serum potassium can have profound effects on electrical activity of the heart. An increase in serum potas-sium, or hyperkalemia, can depolarize the resting mem-brane potential due to changes in EK. If the depolarization is great enough, it can inactivate sodium channels, resulting in increased refractory period duration and slowed impulse propagation. Conversely, a decrease in serum potassium, or hypokalemia, can hyperpolarize the resting membrane potential. This can lead to an increase in pacemaker activity due to greater activation of pacemaker channels, especially in latent pacemakers (eg, Purkinje cells), which are more sensitive to changes in serum potassium than normal pacemaker cells. If one only considers what happens to the potassium electrochemical gradient, changes in serum potassium can also produce effects that appear somewhat paradoxical, especially as they relate to action potential duration. This is because changes in serum potassium also affect the potas-sium conductance (increased potassium increases the con-ductance, decreased potassium decreases the conductance), and this effect often predominates. As a result, hyperkalemiacan reduce action potential duration, and hypokalemiacan prolong action potential duration. This effect of potassium probably contributes to the observed increase in sensitivity to potassium channel-blocking antiarrhythmic agents (quini-dine or sotalol) during hypokalemia, resulting in accentuated action potential prolongation and a tendency to cause torsades de pointes arrhythmia.
FIGURE 14–3 A schematic representation of Na+ channels cycling through different conformational states during the cardiac action potential. Transitions between resting, activated, and inactivated states are dependent on membrane potential and time. The activation gate is shown as m and the inactivation gate as h. Potentials typical for each state are shown under each channel schematic as a function of time. The dashed line indicates that part of the action potential during which most Na+ channels are completely or partially inactivated and unavailable for reactivation.
potassium permeability due to the activity of channels generating transient outward currents.
Although a small fraction of the sodium channels activated during the upstroke may actually remain open well into the later phases of the action potential, sustained depolarization during the plateau (phase 2) is due primarily to the activity of calcium channels. Because the equilibrium potential for calcium, like sodium, is very positive, these channels generate a depolarizing inward current. Cardiac calcium channels activate and inactivate in what appears to be a manner similar to sodium channels, but in the case of the most common type of calcium channel (the “L” type), the transitions occur more slowly and at more positive potentials. After activation, these channels eventually inactivate and the permeability to potassium begins to increase, leading to final repolarization (phase 3) of the action potential. Two types of potassium channels are particularly important in phase 3 repolarization. They generate what are referred to as the rapidly activating (IKr) and slowly activating (IKs) delayed rectifier potassium currents. Repolarization, especially late in phase 3, is also aided by the inward rectifying potassium channels that are responsible for the resting membrane potential.
It is noteworthy that other delayed rectifier-type potassium currents also play important roles in repolarization of certain cardiac cell types. For example, the ultra-rapidly activating delayed rectifier potassium current (IKur) is particularly important in repolarizing the atrial action potential. The resting membrane potential and repolarization of atrial myocytes are also affected by potassium channels that are gated by the parasympathetic neurotransmitter acetylcholine.