Calcium Regulation by the Low-Affinity Taurine Binding Sites of Cardiac Sarcolemma

Several lines of evidence are presented indicating that taurine binding to the low-affinity sites of cardiac sarcolemma is responsible for many previously observed, taurine-mediated pharmacological effects. First, verapamil inhibits taurine binding to the cell membrane in a dose-dependent manner. Second, verapamil reverses taurine enhancement of Ca 2+ binding to the sarcolemma at concentrations at which verapamil itself has no significant effect on Ca 2+ binding. Third, maximal reversal of the negative inotropic effect of both low Ca 2+ and verapamil perfusion occurs at taurine concentrations above the apparent K 0.5 of the low-affinity sites. Fourth, hypotaurine is a potent inhibitor of taurine binding to the low-affinity sites and exerts taurine-like pharmacological effects. This is contrasted with two less potent inhibitors of taurine binding which possess no significant pharmacological activity. It is concluded that binding to low-affinity sarcolemmal sites is a fundamental step in the mechanism underlying the actions of taurine on the heart. The possibility that low-affinity taurine binding affects the Na 2+ /Ca 2+ exchange system of the sarcolemma is discussed.