Binding and movement of calcium in the myocardial cell

This report presents a summary of work done at UCLA over the past 10 years on calcium (Ca) exchange in the myocardium. Four major aspects are considered: binding, permeability, compartmentalization, and transport. Calcium bound within the sarcolemmal-glycocalyx complex plays a significant role in the control of contractile force either in supplying Ca directly to the myofilaments or by serving as a trigger to modulate release from the sarcotubular system. Approximately 80% of bound Ca is associated with sarcolemmal phospholipid. Calcium permeability is controlled at a minimum of two sites--at the glycocalyx and at the lipid bilayer. Removal of sialic acid in cultured cells markedly increases permeability without evidence for disruption of bilayer structure. If, however, the phosphoryl group is cleaved from bilayer phospholipid with phospholipase C, the permeability is also increased. Again, in cultured cells, there is evidence of marked Ca compartmentalization. Surface-bound Ca can participate in excitation-contraction coupling without, in effect, mixing or exchanging with intracellular organelles. If, however, inorganic phosphate (Pi) is added to the perfusion solution, intracellular Ca2+ exchange is markedly augmented. A component of the intracellular Ca2+ is directed to the mitochondria and can be blocked by inhibitors of mitochondrial respiration. Finally, it is clear that Na+ -Ca2+ exchange plays a role in transsarcolemmal Ca2+ transport, with the level of intracellular sodium [Na]i being a most important factor in control of carrier movement under physiological conditions. Elevations of [Na]i will operate to depress Ca2+ efflux and augment Ca2+ influx. Therefore, interventions such as increased frequency or digitalis administration that lead to elevation of [Na]i will be associated with augmented Ca2+ uptake by the myocardium.