Sarcoplasmic reticulum Ca(2+) release by 4-chloro-m-cresol (4-CmC) in intact and chemically skinned ferret cardiac ventricular fibers.
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 Ca(2+) from the sarcoplasmic reticulum was studied in intact cardiac trabeculae and saponin-skinned fibers in which the sarcoplasmic reticulum was loaded with Ca(2+). In intact and saponin-skinned preparations isolated from right ventricle, the effect of 4-CmC on sarcoplasmic reticulum Ca(2+) content was estimated by analysis of caffeine contracture after application of chlorocresol. In addition, the effects of 4-CmC on maximal Ca(2+)-activated tension and the Ca(2+) 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 Ca(2+) release via the ryanodine receptor. Moreover, 4-CmC, like caffeine, has effects on maximal Ca(2+)-activated tension and the Ca(2+) sensitivity of myofibrils.
Laboratoire de Physiologie Générale, Centre National de la Recherche Scientifique, Faculté des Sciences et des Techniques de Nantes, Nantes Cedex 3, France.
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D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003285:Contractile Proteins / Q000378:metabolism; D003408:Cresols / Q000494:pharmacology*; D005289:Ferrets; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D017830:Octoxynol / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
D003285:Contractile Proteins; D003408:Cresols; D019837:Ryanodine Receptor Calcium Release Channel; D012503:Saponins; C006984:chlorocresol; D002110:Caffeine; D017830:Octoxynol; D002118:Calcium