The effects of caffeine and thapsigargin on the contractile force and the action potential in guinea-pig papillary muscles were examined. 2. Caffeine (1 to 10 mM) initially increased contractile force in a concentration-dependent manner. Subsequently, 1 mM caffeine decreased it as compared with precaffeine level (but not significantly). At 5 mM or 10 mM, caffeine also decreased contractile force, but the decrease was still positive as compared with control level. 3. Exchange to low [Ca]o (0.9 mM) or high [K]o (8 mM) decreased steady-state value during exposure to 1 mM caffeine. Addition of 1 microM thapsigargin (TG) decreased the steady-state value during exposure to 1 mM caffeine, but enhanced it with 5 mM and 10 mM caffeine. TG (1 microM) alone increased the force. 4. In electrophysiologic, studies, caffeine shortened the action potential duration (APD) in a concentration-dependent manner. In the presence of caffeine (1 mM), high [K]o shortened APD and decreased the action potential amplitude and resting potential. 5. These results suggest that in the presence of caffeine and/or thapsigargin calcium overload might not occur in the left ventricular papillary muscles of the guinea-pig heart.
