RT Journal Article
SR Electronic
T1 Calcium Regulation by the Low-Affinity Taurine Binding Sites of Cardiac Sarcolemma
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 295
OP 300
VO 17
IS 3
A1 JAMES P. CHOVAN
A1 ELLIOTT C. KULAKOWSKI
A1 STEVEN SHEAKOWSKI
A1 STEPHEN W. SCHAFFER
YR 1980
UL http://molpharm.aspetjournals.org/content/17/3/295.abstract
AB 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 K0.5 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. ACKNOWLEDGMENTS The authors wish to thank Jay Kramer for his technical assistance and Mary Ann Elgin for the typing of the manuscript.