MOLECULAR PHYSIOLOGY OF CARDIAC POTASSIUM CHANNELS

The cardiac action potential results from the complex, but precisely r egulated, movement of ions across the sarcolemmal membrane. Potassium channels represent the most diverse class of ion channels in heart and are the targets of several antiarrhythmic drugs. Potassium currents i n the myocardium can be classified into one of two general categories: 1) inward rectifying currents such as I-KI, I-KACh, and I-KATP; and 2 ) primarily voltage-gated currents such as I-Ks, I-Kr, I-Kp, I-Kar, an d I-to. The inward rectifier currents regulate the resting membrane po tential, whereas the voltage-activated currents control action potenti al duration. The presence of these multiple, often overlapping, outwar d currents in native cardiac myocytes has complicated the study of ind ividual K+ channels; however, the application of molecular cloning tec hnology to these cardiovascular K+ channels has identified the primary structure of these proteins, and heterologous expression systems have allowed a detailed analysis of the function and pharmacology of a sin gle channel type. This review addresses the progress made toward under standing the complex molecular physiology of K+ channels in mammalian myocardium. An important challenge for the future is to determine the relative contribution of each of these cloned channels to cardiac func tion.