THE 1996 MERCK-FROSST-AWARD - THE VOLTAGE-SENSITIVE RELEASE MECHANISM- A NEW TRIGGER FOR CARDIAC CONTRACTION

Contraction in mammalian heart is initiated by a rapid rise in intrace llular free calcium (Ca2+) triggered by excitation of the sarcolemma. Traditional views of cardiac excitation-contraction coupling have focu sed on the importance of Ca2+-induced Ca2+ release from the sarcoplasm ic reticulum as a major source for this increase in Ca2+. Influx of Ca 2+, primarily through L-type Ca2+ channels and the sodium-calcium (Na-Ca2+) exchanger, is considered to be the main trigger for Ca2+-induce d Ca2+ release. However, we recently have discovered a new trigger for excitation-contraction coupling in experiments on isolated ventricula r myocytes under voltage clamp conditions. This trigger is a voltage-s ensitive release mechanism that initiates release of Ca2+ from the sar coplasmic reticulum. This article reviews the development of the conce pt of voltage-activated Ca2+ release in heart and discusses the import ance of this discovery to the physiology, pathophysiology, and pharmac ology of cardiac contraction.