The Control of Ca Release from the Cardiac Sarcoplasmic Reticulum: Regulation Versus Autoregulation

This review discusses the mechanism and regulation of Ca release from the cardiac sarcoplasmic reticulum. Ca is released through the Ca release channel or ryanodine receptor (RyR) by the process of calcium-induced Ca release (CICR). The trigger for this release is the L-type Ca current with a small contribution from Ca entry on the Na-Ca exchange. Recent work has shown that CICR is controlled at the level of small, local domains consisting of one or a small number of L-type Ca channels and associated RyRs. Ca efflux from the s.r. in one such unit is seen as a 'spark' and the properties of these sparks produce controlled Ca release from the s.r. A major factor controlling the amount of Ca released from the s.r. and therefore the magnitude of the systolic Ca transient is its Ca content. The Ca content depends on both the properties of the s.r. and the cytoplasmic Ca concentration. Changes of s.r. Ca content and the Ca released affect the sarcolemmal Ca and Na-Ca exchange currents and this acts to control cell Ca loading and the s.r. Ca content. The opening probability of the RyR can be regulated by various physiological mediators as well as pharmacological compounds. However, it is shown that, due to compensatory changes of s.r. Ca, modifiers of the RyR only produce transient effects on systolic Ca. We conclude that, although the RyR can be regulated, of much greater importance to the control of Ca efflux from the s.r. are effects due to changes of s.r. Ca content.