Cardiac Electrophysiology Review
2000, 4:212–216.
Authors:
CT January and JC Makielski
Section of Cardiology, University of Wisconsin, Madison, WI
Abstract:
To understand cardiac refractoriness it is essential to understand the factors controlling cardiac cell repolarization. While the generation of the action potential upstroke in most cardiac cell types is dependent almost entirely on the transient inward surge of Na+ ions, the plateau (action potential phases 2 and 3) is supported by a delicate balance of many membrane currents (see Figure 1). These include depolarizing slowly decaying late inward Na+ current (INa) and Ca2+ currents (ICa-L and ICa-T), voltage-dependent and Ca2+ activated repolarizing outward currents carried mainly by K+ (the transient outward currents (ITO1 and ITO2), the rapidly (IKr) and slowly (IKs) activating delayed
rectifier K+ currents, and inward rectifier K+ current (IK1)), along with a contribution from electrogenic pump currents (Na+-Ca2+ exchange, Na+-K+ exchange). Furthermore, the balance of currents controlling repolarization differs between atrium and ventricle, regionally within the ventricles, and across the ventricular wall from Purkinje to endocardial, midmyocardial and epicardial cells. Thus, because no single current is dominant, the most complex component of the cardiac action potential is the plateau and terminal repolarization phases. Repolarization is also modulated by many mechanisms including neurohumoral agents (e.g., catecholamines, adenosine, etc.) through intracellular second messenger systems. The integrity of cell-to-cell coupling by gap junctions participates in control of repolarization and can exert large effects on heterogeneity of repolarization. Together, these complex processes control
the QT interval on the ECG. The cardiac action potential and QT interval can be prolonged either by augmenting inward current or by suppressing outward current, or both, and many cardiovascular and non-cardiovascular drugs exert these effects. In addition, the action potential can be prolonged in a number of cardiac disease states including ischemia and reperfusion, heart failure and hypertrophy, as a result of changes in current density and altered channel regulation [1], and in the congenital long QT syndrome as a result of mutations in the genes for Na+ or delayed rectifier K+ channels and certain protein subunits of these channels.