The FASEB Journal, Vol 6, 3092-3100, Copyright © 1992 by The Federation of American Societies for Experimental Biology

REVIEWS

Excitation-contraction coupling in the heart: the state of the question

MD Stern and EG Lakatta
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224.

Recent developments have led to great progress toward determining the mechanism by which calcium is released from the sarcoplasmic reticulum in the heart. The data support the notion of calcium-induced calcium release via a calcium-sensitive release channel. Calcium release channels have been isolated and cloned. This situation creates a paradox, as it has also been found that calcium release is smoothly graded and closely responsive to sarcolemmal membrane potential, properties that would not be expected of calcium-induced calcium release, which has intrinsic positive feedback. There is, therefore, no quantitative understanding of how the properties of the calcium release channel can lead to the macroscopic physiology of the whole cell. This problem could, in principle, be solved by various schemes involving heterogeneity at the ultrastructural level. The simplest of these require only that the sarcolemmal calcium channel be located in close proximity to one or more sarcoplasmic reticulum release channels. Theoretical modeling shows that such arrangements can, in fact, resolve the positive feedback paradox. An agenda is proposed for future studies required in order to reach a specific, quantitative understanding of the functioning of calcium-induced calcium release.

This article has been cited by other articles:

				R. Hilal-Dandan, H. He, J. L. Martin, L. L. Brunton, and W. H. Dillmann Endothelin downregulates SERCA2 gene and protein expression in adult rat ventricular myocytes: regulation by pertussis toxin-sensitive Gi protein and cAMP Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H728 - H734. [Abstract] [Full Text] [PDF]

				S. Ling, J.-Z. Sheng, J. E A Braun, and A. P Braun Syntaxin 1A co-associates with native rat brain and cloned large conductance, calcium-activated potassium channels in situ J. Physiol., November 15, 2003; 553(1): 65 - 81. [Abstract] [Full Text] [PDF]

				G. R. Ferrier and S. E. Howlett Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H1928 - H1944. [Abstract] [Full Text] [PDF]

				R. M Egdell, J. T Milnes, and K. T MacLeod The role of L-type calcium current in the generation of repolarization-induced contraction in cardiac myocytes Cardiovasc Res, October 1, 2000; 48(1): 59 - 67. [Abstract] [Full Text] [PDF]

				V. Lukyanenko and S. Gyorke Ca2+ sparks and Ca2+ waves in saponin-permeabilized rat ventricular myocytes J. Physiol., December 15, 1999; 521(3): 575 - 585. [Abstract] [Full Text] [PDF]

				A. Zahradnikova, I. Zahradnik, I. Gyorke, and S. Gyorke Rapid Activation of the Cardiac Ryanodine Receptor by Submillisecond Calcium Stimuli J. Gen. Physiol., December 1, 1999; 114(6): 787 - 798. [Abstract] [Full Text] [PDF]

				R. El-Hayek, Y. Saiki, T. Yamamoto, and N. Ikemoto A Postulated Role of the Near Amino-terminal Domain of the Ryanodine Receptor in the Regulation of the Sarcoplasmic Reticulum Ca2+ Channel J. Biol. Chem., November 19, 1999; 274(47): 33341 - 33347. [Abstract] [Full Text] [PDF]

				V. Lukyanenko, S. Subramanian, I. Gyorke, T. F Wiesner, and S. Gyorke The role of luminal Ca2+ in the generation of Ca2+ waves in rat ventricular myocytes J. Physiol., July 1, 1999; 518(1): 173 - 186. [Abstract] [Full Text] [PDF]

				V. Lukyanenko, T. F Wiesner, and S. Gyorke Termination of Ca2+ release during Ca2+ sparks in rat ventricular myocytes J. Physiol., March 15, 1998; 507(3): 667 - 677. [Abstract] [Full Text] [PDF]

				R. M Phillips, P. Narayan, A. M Gomez, K. Dilly, L. R Jones, W.J. Lederer, and R. A Altschuld Sarcoplasmic reticulum in heart failure: central player or bystander? Cardiovasc Res, February 1, 1998; 37(2): 346 - 351. [Full Text] [PDF]

				M. Wibo, O. Feron, L. Zheng, M. Maleki, F. Kolar, and T. Godfraind Thyroid status and postnatal changes in subsarcolemmal distribution and isoform expression of rat cardiac dihydropyridine receptors Cardiovasc Res, January 1, 1998; 37(1): 151 - 159. [Abstract] [Full Text] [PDF]

				A. J. Lokuta, M. B. Meyers, P. R. Sander, G. I. Fishman, and H. H. Valdivia Modulation of Cardiac Ryanodine Receptors by Sorcin J. Biol. Chem., October 3, 1997; 272(40): 25333 - 25338. [Abstract] [Full Text] [PDF]

				F. Silvagno, H. Xia, and D. S. Bredt Neuronal Nitric-oxide Synthase-µ, an Alternatively Spliced Isoform Expressed in Differentiated Skeletal Muscle J. Biol. Chem., May 10, 1996; 271(19): 11204 - 11208. [Abstract] [Full Text] [PDF]

				W. Guo, A. O. Jorgensen, L. R. Jones, and K. P. Campbell Biochemical Characterization and Molecular Cloning of Cardiac Triadin J. Biol. Chem., January 5, 1996; 271(1): 458 - 465. [Abstract] [Full Text] [PDF]

				J. R. Patel, R. Coronado, and R. L. Moss Cardiac Sarcoplasmic Reticulum Phosphorylation Increases Ca2+ Release Induced by Flash Photolysis of Nitr-5 Circ. Res., November 1, 1995; 77(5): 943 - 949. [Abstract] [Full Text]