Cardiac Ion Channels

Abstract

The analysis of the molecular basis of the inherited cardiac arrhythmias has been the driving force behind the identification of the ion channels that generate the action potential. The genes encoding all the major ion channels have cloned and sequenced. The studies have revealed greater complexity than heretofore imagined. Many ion channels function as part of macromolecular complexes in which many components are assembled at specific sites within the membrane. This review describes the generation of the normal cardiac action potential. The properties of the major ionic currents are the examined in detail. Special emphasis is placed on the functional consequences of arrhythmia-associated ion channel mutations. The review concludes with a glimpse of the directions in which this new electrophysiology may lead. The normal sequence and synchronous contraction of the atria and ventricles require the rapid activation of groups of cardiac cells. An activation mechanism must enable rapid changes in heart rate and also respond to the changes in autonomic tone. The propagating cardiac action potential fulfils these roles. Figure 1 illustrates the 5 phases of the normal action potential: 1. Phase 4, or the resting potential, is stable at ≈−90 mV in normal working myocardial cells. 2. Phase 0 is the phase of rapid depolarization. The membrane potential shifts into positive voltage range. This phase is central to rapid propagation of the cardiac impulse (conduction velocity, θ=1 m/s). 3. Phase 1 is a phase of rapid repolarization. This phase sets the potential for the next phase of the action potential. 4. Phase 2, a plateau phase, is the longest phase. It is unique among excitable cells and marks the phase of calcium entry into the cell. 5. Phase 3 is the phase of rapid repolarization that restores the membrane potential to its resting value.1 Figure 1. Membrane currents that generate the a normal …