Interaction between Caffeine and Adenosine on the Membrane Current and Tension Component in the Bullfrog Atrial Muscle

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Abstract
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 and slow inward current (Is). At higher concentrations it elicited an increase of the delayed outward current (Ix). The augmentation of Is was principally due to increase of the limiting conductance (.hivin.gs), while the activation and inactivation variables (d.infin., f.infin.) 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 (INaf [Na fast current], Is, Ix and background inward current, Ib) and tension components (ICa[Ca current]-dependent and independent tensions). The inhibition of Is was due to a decrease of .hivin.gs and no appreciable change was seen in d.infin. and f.infin.. Apparently adenosine has a strong stabilizing action on the myocardium, especially when the heart muscle activity is accelerated by increased cyclic AMP.