Caffeine altered cardiac myofilament activity by increasing submaximal and depressing maximal force independently of Ca2+ binding to troponin C, likely via direct effects on actin-myosin interaction.
Caffeine alters cardiac myofilament function via a mechanism independent of troponin C-Ca2+ binding, potentially involving direct effects on actin-cross-bridge interaction.
We investigated the mechanism by which caffeine influences myofilament responsiveness to Ca2+ by measuring isometric force, Ca2+ binding, and ATPase activity of dog cardiac myofilament proteins. Caffeine (20 mM) increased submaximal and depressed maximal force in skinned fiber bundles. Although the Ca2+ sensitivity of myofilament activity was increased by caffeine, there was no effect on Ca2+ binding to troponin C (TnC) in skinned fiber bundles. To determine if caffeine altered actin-myosin interaction or affected myosin directly, myofibrillar, actomyosin, and myosin ATPase activities were measured. Maximal Ca(2+)-activated myofibrillar Mg(2+)-ATPase activity was depressed by 20 mM caffeine, whereas submaximal Mg(2+)-ATPase activities were not changed. Actomyosin Mg(2+)-ATPase activity was significantly depressed by caffeine concentrations > or = 15 mM. Myosin Ca(2+)-ATPase activity was depressed by caffeine, whereas Mg(2+)-ATPase and K(EDTA)-ATPase activities were not affected. These data suggest that caffeine affects myofilament function via a mechanism that is independent of TnC-Ca2+ binding but that may involve direct effects on actin-cross-bridge interaction.
Powers et al. (Thu,) reported a other. Caffeine was evaluated on Myofilament responsiveness to Ca2+ (isometric force, Ca2+ binding, and ATPase activity). Caffeine altered cardiac myofilament activity by increasing submaximal and depressing maximal force independently of Ca2+ binding to troponin C, likely via direct effects on actin-myosin interaction.