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Vol. 290, Issue 2, 578-586, August 1999

Sarcoplasmic Reticulum Ca2+ Release by 4-Chloro-m-Cresol (4-CmC) in Intact and Chemically Skinned Ferret Cardiac Ventricular Fibers

S. Choisy, C. Huchet-Cadiou and C. Léoty

Laboratoire de Physiologie Générale, Centre National de la Recherche Scientifique, Faculté des Sciences et des Techniques de Nantes, Nantes Cedex 3, France

The purpose of this study was to determine whether 4-chloro-m-cresol (4-CmC) could generate caffeine-like responses in ferret cardiac muscle. The concentration dependence of 4-CmC-mediated release of Ca2+ from the sarcoplasmic reticulum was studied in intact cardiac trabeculae and saponin-skinned fibers in which the sarcoplasmic reticulum was loaded with Ca2+. In intact and saponin-skinned preparations isolated from right ventricle, the effect of 4-CmC on sarcoplasmic reticulum Ca2+ content was estimated by analysis of caffeine contracture after application of chlorocresol. In addition, the effects of 4-CmC on maximal Ca2+-activated tension and the Ca2+ sensitivity of myofibrils were analyzed by using Triton-skinned cardiac fibers. The results show that 4-CmC generates a contractile response in saponin-skinned but not intact fibers. The sarcoplasmic reticulum is implicated in the 4-CmC response; more precisely, in Ca2+ release via the ryanodine receptor. Moreover, 4-CmC, like caffeine, has effects on maximal Ca2+-activated tension and the Ca2+ sensitivity of myofibrils.

0022-3565/99/2902-0578$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


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