ABSTRACT Electrical activity is a fundamental phenomenon of living cardiac cells. The normal function of the heart relies on normal electrical activity of the heart itself. Cardiac electrical disorders are a cause of considerable morbidity and morality. Although tremendous efforts have been made to improve the therapeutic outcome of arrhythmias, current treatments are still inadequate. Part of the reason is our insufficient understanding of the nature of the ion channel proteins and the mechanisms by which these channel proteins govern the electrical activity of the heart at the molecular level. Because of this, ever-growing efforts are being made to exploit unsolved mysteries and to fight new problems, by researchers from all over the world with their talent, their elegant approaches, and their sophisticated techniques. In particular, studies utilizing human cardiac preparations have yielded enormous amount of useful information awaiting for integral analysis so that it could be applied to clinical medicine and drug development. This review article attempts to compile and summarize work that the author was involved in and work completed by other researchers. Characteristics of human cardiac AP are introduced, with emphasis on the interspecies differences and regional variations. Pathological alterations and pharmacological properties of human AP are also described. Basic biophysical properties of five major repolarizing K+ currents (Ito1, IKur, IKr, IKs, and IK1) and their physiological roles and pathological alterations are summarized. Studies on the potential molecular composition of these native K+ channels are mentioned. And finally, the potential implications of studies on the ionic mechanisms and molecular basis in new drug development for treatment of cardiac electrical disorders are discussed. The goal of this article is to try to help researchers and pharmaceutical companies to make full use of information provided by recent advance in molecular biology.
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