Molecular Physiology of Cardiac Repolarization

作者：Jeanne M. Nerbonne, Robert S. Kass · 发表于：Physiological Reviews · 年份：2005 · DOI：10.1152/physrev.00002.2005 · 被引用次数：1069 · 研究领域：Cardiac electrophysiology and arrhythmias、Ion channel regulation and function、Neuroscience and Neuropharmacology Research

The heart is a rhythmic electromechanical pump, the functioning of which depends on action potential generation and propagation, followed by relaxation and a period of refractoriness until the next impulse is generated. Myocardial action potentials reflect the sequential activation and inactivation of inward (Na(+) and Ca(2+)) and outward (K(+)) current carrying ion channels. In different regions of the heart, action potential waveforms are distinct, owing to differences in Na(+), Ca(2+), and K(+) channel expression, and these differences contribute to the normal, unidirectional propagation of activity and to the generation of normal cardiac rhythms. Changes in channel functioning, resulting from inherited or acquired disease, affect action potential repolarization and can lead to the generation of life-threatening arrhythmias. There is, therefore, considerable interest in understanding the mechanisms that control cardiac repolarization and rhythm generation. Electrophysiological studies have detailed the properties of the Na(+), Ca(2+), and K(+) currents that generate cardiac action potentials, and molecular cloning has revealed a large number of pore forming (alpha) and accessory (beta, delta, and gamma) subunits thought to contribute to the formation of these channels. Considerable progress has been made in defining the functional roles of the various channels and in identifying the alpha-subunits encoding these channels. Much less is known, however, about the functioning ...