The Regulation of the Ca-Pumping Activity of Cardiac Sarcoplasmic Reticulum by Calmodulin

The rapid regulation of the cytosolic free calcium concentration in striated muscles is under the control of the sarcoplasmic reticulum (SR) activity. The major protein constituent of the SR membrane is a calcium-dependent ATPase of molecular mass 110,000, whose activity is coupled with the vectorial translocation of calcium ions from the cytosol into the compartment enclosed by the membranes. This transport activity is responsible for the relaxation of the myofibrils in striated muscles. During the process of excitation-contraction coupling, calcium ions, stored against a large concentration gradient inside the SR compartment, are readily mobilized and flow back to the cytosol, thus inducing contraction. In this process, electrical stimuli travelling along the T-tubular system during the action potential, and/or intracellular chemical messengers (such as inositoltriphosphate or calcium), released in the vicinity of the terminal cisterne of the SR network, are assumed to induce the transient opening of putative calcium channels located on the SR membrane. Regulatory mechanisms of the calcium fluxes across the SR membrane play a major role in the regulation and modulation of the mechanical activity of muscle cells. cAMP is a well-known modulator of myocardial contractility. The effect of this intracellular messenger is achieved, at least in part, by augmenting calcium transport into the SR. A stimulation of the calcium pump is expected to increase both the rate of relaxation of the muscle cells and the amount of calcium ions stored in the SR compartment. More calcium ions can be released to the myofibrils upon excitation, thus increasing the force of contraction.