Effects of caffeine on tension development in dog papillary muscle under voltage clamp.

1. Effects of caffeine on tension in the dog papillary muscle were investigated using a voltage clamp with the double sucrose-gap method. 2. An S-shaped relationship between membrane potential and developed tension was obtained in Tyrode solution. An increase of the external calcium concentration produced an upward shift of the relationship and a decrease of calcium, a downward shift. 3. Caffeine (10 mM/liter) reduced the peak tension at inside positive potentials in Tyrode solution, but scarcely changed the tension at inside negative potentials. 4. An administration of caffeine retarded the relaxation phase at first, but the contraction phase was also gradually slowed. 5. The magnitude of tension elicited by an action potential after repetitive voltage clamp pulses was dependent on the magnitude of tension during prior clamp pulses in Tyrode solution, but the dependency disappeared in caffeine-treated preparations. 6. It was suggested that a tension development in the dog papillary muscle is largely regulated by the sarcoplasmic reticulum and that caffeine reduces the amounts of Ca taken up by and released from the reticulum.