Control of cardiac contractility at the cellular level.

Abstract

Recent experiments involving the measurement of intracellular activities in Na+ and Ca2+; functional studies; descriptions of the Na+ and Ca2+ fluxes from intact cardiac tissue; studies of isolated cardiac sarcolemmal vesicles, isolated sarcoplasmic reticulum (SR) vesicles, and isolated mitochondria; and investigations of the behavior of cardiac contractile proteins have revealed a plurality of processes associated with the activation and control of the contraction and relaxation of cardiac muscle. Which of these processes predominates, even in intact cardiac muscle, would seem to depend critically on the experimental conditions. As the cycle of contraction and relaxation essentially involves the reversible binding of Ca2+ to the contractile proteins as a final step, if a number of processes influence this binding they must interact. Quantitative consideration of available information suggests that in the beating mammalian heart the bulk of the activating Ca2+ cycles between the SR and the contractile proteins with the sarcolemmal Ca2+ pump and Na+-Ca2+ exchange operating to maintain the Ca2+ economy of the heart and affecting contraction only by influencing the filling of the SR with Ca2+ and possibly its release. In amphibian heart the sarcolemmal Na+-Ca2+ exchange would seem to be more directly involved, adding or subtracting from the Ca2+ liberated from the SR. The Ca2+ uptake by mitochondria may become particularly important when the intracellular sodium concentration alters.