Some effects of organic anions on excitability and excitation–contraction coupling in frog skeletal muscle

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Abstract
When substituted for external chloride, organic anions differed markedly from one another in the extent to which they produced hyperexcitability and in the direction and intensity of their effects on twitch tension in frog skeletal muscle. All of the anions studied reduced the threshold [K]0 for K contractures and most enhanced twitch tension. Among carboxylate anions, increasing the size of the attached apolar hydrocarbon chain led to decreased hyperexcitability and to reduction in the amplitude of twitches and maximum K-contractures, butyrate being the most effective depressant of these responses. Sulfonate anions produced much less conspicuous changes in contractile performance. With γ-hydroxybutyrate, the introduction of a polar group on the hydrocarbon terminus resulted in twitch enhancement and partial restoration of maximum K-contracture tension. The depressant effect of butyrate on K contractures was partially overcome by a fivefold increase in the external concentration of calcium but twitches were unaffected. Perchlorate (12 mM) effectively antagonized the depressant actions of butyrate on twitches as well as K contractures. Most of the effects of these anions were prompt in onset. Impairment of contractile performance by butyrate was not accompanied by appreciable changes in membrane resting or action potentials or in the relation between [K]0 and membrane potential, and took place in spite of reduction in K-contracture threshold. Such effects must result from alteration in excitation–contraction coupling, possibly by interference with the binding of divalent cations to the membrane surface.