Abstract
There are four cellular Ca transport systems which compete to remove Ca from the myoplasm in mammalian ventricular myocytes. These are 1) the SR Ca-ATPase, 2) the sarcolemmal Na-Ca exchange, 3) the sarcolemmal Ca-ATPase and 4) the mitochondrial Ca uniporter. Using multiple experimental approaches we have evaluated the dynamic interaction of these systems during the normal cardiac contraction-relaxation cycle. The SR Ca-ATPase and Na-Ca exchange are clearly the most important, quantitatively; however, the relative roles vary in a species-dependent manner. In particular, the SR is much more strongly dominant in rat ventricular myocytes, where approximately 92% of Ca removal is via SR Ca-ATPase and only 7% via Na-Ca exchange during a twitch. In other species (rabbit, ferret, cat, and guinea pig) the balance is more in the range of 70% SR CA-ATPase and 25-30% Na-Ca exchange. Ferret ventricular myocytes also exhibit an unusually strong sarcolemmal Ca-ATPase. During the steady state the same amount of Ca must leave the cell as enters over a cardiac cycle. This implies that 25-30% of the Ca required to activate contraction must enter the cell, and experiments demonstrate that this amount of Ca may be supplied by the L-type Ca current.
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