AJP - Cell Physiology, Vol 245, Issue 1 1-14, Copyright © 1983 by American Physiological Society

ARTICLES

Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum

A. Fabiato

The hypothesis of a Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) is supported by experiments done in skinned cardiac cells (sarcolemma removed by microdissection). According to this hypothesis, the transsarcolemmal Ca2+ influx does not activate the myofilaments directly but through the induction of a Ca2+ release from the SR. The stimulus gating CICR is not a small change in free Ca2+ concentration (delta[free Ca2+]) outside the SR but a function of the rate of this change (delta[free Ca2+/delta t]). The initial relatively fast component of the transsarcolemmal Ca2+ current would trigger Ca2+ release; the subsequent slow component, perhaps corresponding to noninactivating Ca2+ channels, would load the SR with an amount of Ca2+ available for release during subsequent beats. Inactivation of CICR is caused by the large increase of [free Ca2+] outside the SR resulting from Ca2+ release, which inhibits further release. This negative feedback helps to explain that CICR is not all or none. During relaxation the Ca2+ reaccumulation in the SR is backed up by the Ca2+ efflux across the sarcolemma through Na+-Ca2+ exchange and the sarcolemmal Ca2+ pump. Computations of the Ca2+ buffering in the mammalian ventricular cell and of the systolic transsarcolemmal Ca2+ influx do not support the alternative hypothesis that this influx of Ca2+ is large enough to activate the myofilaments directly. Yet the hypothesis of a CICR can be challenged because of many problems and uncertainties related to the preparations and methods used for skinned cardiac cell experiments.

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				Y. M. Usachev and S. A. Thayer All-or-None Ca2+ Release from Intracellular Stores Triggered by Ca2+ Influx through Voltage-Gated Ca2+ Channels in Rat Sensory Neurons J. Neurosci., October 1, 1997; 17(19): 7404 - 7414. [Abstract] [Full Text] [PDF]

				P. Tarroni, D. Rossi, A. Conti, and V. Sorrentino Expression of the Ryanodine Receptor Type 3 Calcium Release Channel during Development and Differentiation of Mammalian Skeletal Muscle Cells J. Biol. Chem., August 8, 1997; 272(32): 19808 - 19813. [Abstract] [Full Text] [PDF]

				L. A. Blatter, J. Huser, and E. Rios Sarcoplasmic reticulum Ca2+ release flux underlying Ca2+ sparks in cardiac muscle PNAS, April 15, 1997; 94(8): 4176 - 4181. [Abstract] [Full Text] [PDF]

				R. Zucchi and S. Ronca-Testoni The Sarcoplasmic Reticulum Ca2+ Channel/Ryanodine Receptor: Modulation by Endogenous Effectors, Drugs and Disease States Pharmacol. Rev., March 1, 1997; 49(1): 1 - 52. [Abstract] [Full Text] [PDF]

				L. Xu, G. Mann, and G. Meissner Regulation of Cardiac Ca2+ Release Channel (Ryanodine Receptor) by Ca2+, H+, Mg2+, and Adenine Nucleotides Under Normal and Simulated Ischemic Conditions Circ. Res., December 1, 1996; 79(6): 1100 - 1109. [Abstract] [Full Text]