Sarcoplasmic reticulum Ca2+ 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 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.