Myocardial calcium compartmentation

Abstract

The mammalian cardiac myocyte contains ~1600 μmol 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 μmo/L cell water via the sarcolemmal "L" Ca channel, resulting in the secondary release of 50-60 μnol from the sarcoplasmic reticulum (SR) compartment, which contains 500 μmol in the junctional (JSR) plus corbular (CSR) components. Maximal contraction in 8 mM[Ca](0) is associated with SR release of 130 μmol triggered by entry of only 8-14 μmol 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 μM 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 μmol) is present, and its contribution to cellular flux is clearly identified in the intact cell. Its low flux rate (1 μmol 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 μmol/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.