Role of calcium in heart metabolism

The role of calcium in modulating the activity of enzymes and transport pathways in heart muscle is briefly reviewed, with emphasis on its participation in the modulation of sarcolemmal glucose transport, which is normally the rate-limiting step in glucose utilization. Evidence for and against the "calcium hypothesis" of glucose transport regulation is discussed. Data from isolated myocardial preparations are presented to illustrate the dependence of glucose transport on Ca2+ and the role of this ion in coupling changes in cellular activity and metabolism to appropriate adjustments in the transport rate. It is shown that glucose transport is stimulated when cytosolic Ca2+ levels are raised, e.g., by activation of sarcolemmal Na+-Ca2+ exchange, by beta-adrenergic agents, by muscular contraction and inotropic interventions, and by intracellular Ca2+ release from the sarcoplasmic reticulum and the mitochondria. Stimulation of transport by insulin is also partially Ca2+ dependent. The main negative feedback on glucose transport is from the oxidation of fatty acids, ketone bodies, etc., and it is suggested that alterations in mitochondrial Ca2+ fluxes may be responsible.