Effect of caffeine on the birefringence signal in single skeletal muscle fibers and mammalian heart. Possible mechanism of action.

Effects of caffeine on single fibers of frog (Rana pipiens) toe muscle and rabbit atrial trabeculae were investigated by measuring action potential, tension and the E-C coupling-related birefringence signal. Caffeine in concentrations of 1.0 to 2.0 mmol/l potentiated the twitch, prolonged the action potential, delayed the onset and suppressed the rate of the birefringence signal in skeletal muscle fibers. In heart muscle, caffeine at concentrations of 2-10 mmol/l potentiated tension and suppressed the second component of the birefringence signal. Although theophylline also potentiated tension and suppressed the rate of rise of the birefringence signal, other diesterase inhibitors, Ro7-2956, or stimulators of adenylate cyclase system such as dibutyryl cAMP or adrenaline failed to alter the birefringence signal while potentiating tension. Since the second component of the birefringence signal has been associated with Ca2+-releasing activity of the sarcoplasmic reticulum, the suppression of this signal and the simultaneous potentiation of tension by caffeine suggests that either caffeine depresses the rate of Ca2+ release or that the birefringence signal is not associated directly with Ca2+ release, rather with Ca2+ uptake. In either case, the results suggest that potentiation of tension by caffeine may be mediated by suppression of the Ca2+ reuptake process.