MYOCARDIAL CALCIUM COMPARTMENTATION

The mammalian cardiac myocyte contains similar to 1600 mu mol of exchangeable Ca per liter of cell water. Normal contractile function requires that this exchangeable content be rigorously compartmentalized. A contraction in 1 mM[Ca](0) is triggered by entry of only 6-10 mu mol/L cell water via the sarcolemmal ''L'' Ca channel, resulting in the secondary release of 50-60 mu mol from the sarcoplasmic reticulum (SR) compartment, which contains 500 mu mol in the junctional (JSR) plus corbular (CSR) components. Maximal contraction in 8 mM[Ca](0) is associated with SR release of 130 mu mol triggered by entry of only 8-14 mu mol via the Ca channel. This indicates the marked amplification ability of the SR-compartmentalized Ca. Ca efflux occurs via the sarcolemmal Na-Ca exchanger, which transports Ca from a newly identified Na-Ca exchange-dependent compartment. Current studies indicate that this compartment is localized to inner sarcolemmal leaflet anionic phospholipids (PLs) in equilibrium with JSR Ca. A recently developed model indicates that the presence of anionic PLs in this restricted space maintains Ca concentration > 20 mu M for > 200 ms after JSR release, so as to maintain an optimal environment for the operation of the Na-Ca exchanger. A large mitochondrial compartment (400 mu mol) is present, and its contribution to cellular flux is clearly identified in the intact cell. Its low flux rate (1 mu mol Ca/L cell water/s) is consistent with the generally accepted role for Ca in the control of dehydrogenase-related mitochondrial metabolism. The largest single compartment (600 mu mol/L cell water) is the most rapidly exchangeable and is largely lanthanum displaceable, which indicates that it is predominantly sarcolemma bound. It provides a large buffer at the membrane with a portion of its Ca possibly interacting with the ca channel and Na-Ca exchanger.