Caffeine treatment inhibits drug-induced calcium release from sarcoplasmic reticulum and caffeine contracture but not tetanus in frog skeletal muscle

Abstract

Effects of pretreatment with caffeine on Ca²⁺ release induced by caffeine, thymol, quercetin, or p-chloromercuriphenylsulfonic acid (pCMPS) from the heavy fraction of sarcoplasmic reticulum (SR) were studied and compared with those effects on caffeine contracture and tetanus tension in single fibers of frog skeletal muscle. Caffeine (1–5 mM) did induce transient Ca²⁺ release from SR vesicles, but subsequent further addition of caffeine (10 mM, final concentration) induced little Ca²⁺ release. Ca²⁺ release induced by thymol, quercetin, or pCMPS was also inhibited by pretreatment with caffeine. In single muscle fibers, pretreatment with caffeine (1–5 mM) partially reduced the contracture induced by 10 mM caffeine. However, tetanus tension was almost maximally induced by electrical stimulus in caffeine-treated fibers. These results indicate that SR, which becomes less sensitive to caffeine, thymol, quercetin, or pCMPS by pretreatment with caffeine, can still respond to a physiological signal transmitted from transverse tubules.Key words: Ca²⁺ release, sarcoplasmic reticulum, caffeine, tetanus, skeletal muscle.