Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction

• Published in: American journal of physiology. Heart and circulatory physiology 2001-05, Vol.280 (5), p.H1928-H1944
• Main Authors: Ferrier, Gregory R, Howlett, Susan E
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium Channels - physiology; Humans; Membrane Potentials - physiology; Myocardial Contraction - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2001.280.5.H1928

Cardiovascular Research Laboratories, Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7 The steps that couple depolarization of the cardiac cell membrane to initiation of contraction remain controversial. Depolarization triggers a rise in intracellular free Ca 2+ which activates contractile myofilaments. Most of this Ca 2+ is released from the sarcoplasmic reticulum (SR). Two fundamentally different mechanisms have been proposed for SR Ca 2+ release: Ca 2+ -induced Ca 2+ release (CICR) and a voltage-sensitive release mechanism (VSRM). Both mechanisms operate in the same cell and may contribute to contraction. CICR couples the release of SR Ca 2+ closely to the magnitude of the L-type Ca 2+ current. In contrast, the VSRM is graded by membrane potential rather than Ca 2+ current. The electrophysiological and pharmacological characteristics of the VSRM are strikingly different from CICR. Furthermore, the VSRM is strongly modulated by phosphorylation and provides a new regulatory mechanism for cardiac contraction. The VSRM is depressed in heart failure and may play an important role in contractile dysfunction. This review explores the operation and characteristics of the VSRM and CICR and discusses the impact of the VSRM on our understanding of cardiac excitation-contraction coupling. voltage-sensitive release mechanism; calcium-induced calcium release; heart failure; phosphorylation; sarcoplasmic reticulum