Molecular Pharmacology, Vol 17, 295-300, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

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

¹ Center for Health Sciences, Division of Biochemistry and Biophysics, Lehigh University, Bethlehem, Pennsylvania 18015
² Center for Health Sciences, Division of Biochemistry and Biophysics, Lehigh University, Bethlehem, Pennsylvania 18015, and Department of Physiology and Biophysics, Hahnemann Medical College, Philadelphia, Pennsylvania 19102

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 Ca²⁺ binding to the sarcolemma at concentrations at which verapamil itself has no significant effect on Ca²⁺ binding. Third, maximal reversal of the negative inotropic effect of both low Ca²⁺ 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 Na²⁺/Ca²⁺ exchange system of the sarcolemma is discussed.

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ACKNOWLEDGMENTS The authors wish to thank Jay Kramer for his technical assistance and Mary Ann Elgin for the typing of the manuscript.

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