Membrane control of cardiac contractility

Abstract

ALL myocardial cells contract in every cardiac cycle and the contractility of the heart cannot be modulated as in skeletal muscle by varying the number of active cells, so each cardiac cell must be capable of a broad range of contractile states. Such versatility could result from changes in the action potential, in the amount of Ca²⁺ released for activation of the contraction, or in the contractile proteins themselves. Phosphorylation of the inhibitory subunit of troponin seems to occur in parallel with the increase in contractility of isolated hearts perfused with catecholamines^1,2, and studies using isolated proteins indicate that the phosphorylation may be associated with a change in ATPase activity^3,4, but a direct demonstration that the functional properties of contractile proteins themselves can be altered in a manner compatible with a physiologically important regulatory mechanism has not yet been produced. We report here studies of cardiac cells with membranes that have been made hyperpermeable, in which the response of the contractile system to Ca ions, the presumed trigger for activation of contraction, may be altered markedly with respect to both the concentration of calcium required for activation and the maximum generated force by the microenvironment of the contractile proteins and by reactions involving the cell's membranes. Cyclic nucleotides may be involved in some of these regulatory reactions.