An analysis of the subsynaptic site of action of theophylline on isolated cat tenuissimus muscle.

The subsynaptic actions of theophylline were studied by employing intracellular recording techniques in the isolated cat tenuissimus muscle. Theophylline produced a dose-dependent increase in miniature end-plate potential (MEPP) amplitude. The maximal increase (30%) in MEPP amplitude occurred at the 1.8 mM concentration of theophylline with a concomitant depolarization of the resting membrane potential. Depolarizations induced by acetylcholine were potentiated by 1.8 mM theophylline. This effect was less evident with a carbachol-induced depolarization, which indicates a possible anticholinesterase action. Input resistance decreased significantly; this effect correlated with the decline in resting membrane potential produced by theophylline. The equilibrium potential of the EPP was shifted to a more positive value in a reversible manner. In addition, the conductance change due to MEPPs, acetylcholine and carbachol was increased by theophylline treatment. These results suggest that the shift in equilibrium potential of the EPP coupled with a slight anticholinesterase action may account for the increase in MEPP amplitude observed with theophylline treatment.