The effects of caffeine on the contraction of the frog heart.

1. The force of contraction and the membrane potentials have been measured from preparations of frog heart, with methods that also allow the rapid exchange of the extracellular fluid.2. In regularly beating preparations, caffeine induces only weak contractures at temperatures above 15 degrees C, but it does cause a marked potentiation of the twitch responses; longer exposure results in a depression of contraction. The build up and decline of the twitch strength, on addition and on removal of caffeine approximates to a single exponential, time constant 26-45 sec, and this time constant is not altered by variation of the Ca, the stimulus rate or the caffeine concentration. This time course of the change of twitch strength is less complex than the changes seen when either Ca or the stimulus rate is altered, suggesting a more direct action of caffeine on excitation-contraction coupling.3. Caffeine increases the strength of the contractures initiated by potassium-rich or sodium-depleted solutions in isolated atrial trabeculae.4. After the spontaneous relaxation of the contracture, evoked by either sodium-free or potassium-rich fluids, the application of caffeine initiates a redevelopment of tension. This caffeine contracture is transient and its strength is dependent on the caffeine concentration. The response in sodium-free solution can be elicited in the virtual absence of extracellular calcium.5. Local anaesthetics antagonize the caffeine contracture.6. The results suggest that the sarcoplasmic reticulum of frog heart muscle plays an important role in the initiation and control of contraction and relaxation.