The voltage-sensitive release mechanism: a new trigger for cardiac contraction

Abstract

Contraction in mammalian heart is initiated by a rapid rise in intracellular free calcium (Ca2+) triggered by excitation of the sarcolemma. Traditional views of cardiac excitation–contraction coupling have focused on the importance of Ca2+-induced Ca2+ release from the sarcoplasmic reticulum as a major source for this increase in Ca2+. Influx of Ca2+, primarily through L-type Ca2+ channels and the sodium–calcium (Na+–Ca2+) exchanger, is considered to be the main trigger for Ca2+-induced Ca2+ release. However, we recently have discovered a new trigger for excitation–contraction coupling in experiments on isolated ventricular myocytes under voltage clamp conditions. This trigger is a voltage-sensitive release mechanism that initiates release of Ca2+ from the sarcoplasmic reticulum. This article reviews the development of the concept of voltage-activated Ca2+ release in heart and discusses the importance of this discovery to the physiology, pathophysiology, and pharmacology of cardiac contraction.