Transient outward potassium current and Ca2+ homeostasis in the heart: beyond the action potential
Abstract
The present review deals with Ca2+-independent, K+-carried transient outward current (Ito), an important determinant of the early repolarization phase of the myocardial action potential. The density of total Ito and of its fast and slow components (I(to,f) and I(to,s), respectively), as well as the expression of their molecular correlates (pore-forming protein isoforms Kv4.3/4.2 and Kv1.4, respectively), vary during postnatal development and aging across species and regions of the heart. Changes in Ito may also occur in disease conditions, which may affect the profile of cardiac repolarization and vulnerability to arrhythmias, and also influence excitation-contraction coupling. Decreased Ito density, observed in immature and aging myocardium, as well as during several types of cardiomyopathy and heart failure, may be associated with action potential prolongation, which favors Ca2+ influx during membrane depolarization and limits voltage-dependent Ca2+ efflux via the Na+/Ca2+ exchanger. Both effects contribute to increasing sarcoplasmic reticulum (SR) Ca2+ content (the main source of contraction-activating Ca2+ in mammalian myocardium), which, in addition to the increased Ca2+ influx, should enhance the amount of Ca2+ released b...Continue Reading
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