Increased sensitivity of frog skeletal muscle to procaine in the presence of organic anions.

In solutions containing an organic anion in place of chloride, frog toe muscles displayed increased sensitivity to the local anaesthetic action of procaine. Twitch inhibition by procaine in all media was accompanied by suppression of action potentials without change in membrane resting potentials. The twitch depressant effect of procaine was greater in solutions with carboxylate anions than with alkyl sulfonates. The intensity and the rapidity of onset of the effects of organic anions was related to the size of their hydrophobic component. Procaine accentuated acetate-induced reductions in the [K]0 required to produce K contractures and in the time course of submaximum K contractures. These effects were not shared by benzocaine. They were antagonized by increased [Ca]0. The results indicate that separate agents can exert mutually enhancing actions from opposite surfaces of the sarcolemma to facilitate the inactivation of depolarization-induced excitation--contraction coupling as well as that of the potential-dependent sodium channel.