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 intracellular free calcium (Ca2+) triggered by excitation of the sarcolemma. Traditional views of cardiac excitation-contraction coupling have focused on the importance of Ca(2+)-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 Ca(2+)-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.
Howlett
S E
SE
Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
Ferrier
G R
GR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D006321:Heart / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D013696:Temperature
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D002118:Calcium