Antagonistic action of caffeine and adenosine were studied at the membrane current and tension component levels in myocardium of the bullfrog atrium, mainly under voltage clamp using the double sucrose-gap method.
Caffeine (1-5 mM) produced marked augmentation of the phasic and tonic tensions as well as slow inward current (I_s). At higher concentrations it elicited an increase of the delayed outward current (I_x). The augmentation of Is was principally due to increase of the limiting conductance (g_s), while the activation and inactivation variables (d∞, f∞) were not changed significantly. The dose-tension response curve for caffeine, which appeared sigmoidal, was notably lowered in the presence of adenosine (1-3 mM), indicating a competitive type of inhibition. Adenosine, in the presence of caffeine, exerted a narcotic-like action by inhibiting all of the membrane currents (I_Naf, I_s, I_x and background inward current, I_b) and tension components (I_ca-dependent and independent tensions). The inhibition of I_s was due to a decrease of gs and no appreciable change was observed in d∞ and f∞. These results suggest that adenosine has a strong stabilizing action on the myocardium, especially when the heart muscle activity is accelerated by increased cyclic AMP.