A comparison of the effects of cationic, anionic, and neutral amphipathic agents on the contractile behaviour of frog skeletal muscle. II. Amplitude of depolarization and repolarization-induced contractures

Abstract

Sufficiently high concentrations of cationic (n-alkyl trimethylammonium) or neutral (n-alkanols) amphipathic agents reduced the amplitude of maximum K contractures of frog toe muscles, an effect which was antagonized by reduced temperature, by the presence of perchlorate anions, or (to a lesser extent) by an increased concentration of divalent cations. Enhancement of the similar effect of tetracaine was prominent only with alkyl trimethylammonium compounds. Enhancement of the depressant effect of acidity (pH 5.0) was observed with octyl trimethylammonium and octanol but not with octanesulfonate or butanol. Partial restoration of potassium contractures in media lacking divalent cations was produced by octane- or nonane-sulfonate and by propanol but not by octyl trimethylammonium or octanol. The alkyl sulfonates differed from the other agents studied in producing tonic contractures at concentration which did not reduce maximum K-contracture tension. The alkyl sulfonates also differed from other amphipaths of similar size in their ability to elicit small repolarization-induced contractures in the absence of perchlorate, although this property also was shared by small alkanols. Sufficient concentrations of all amphipaths reduced the amplitude of repolarization-induced contractures in the presence of perchlorate. The intensity of the effects of these agents on contractile function usually was proportional to the size of their apolar group, and with ionic apmphipaths such effects were apparent only with compounds having hydrocarbon chains containing eight or more carbon atoms. These experiments indicate that hydrophobic interactions in the external lamina of the sarcolemma can influence the potential-dependent control of contractile function in skeletal muscle, presumably by effects on the conformational transitions of integral membrane proteins. The similarity between many of the effects of alkyl sulfonate and small n-alkanols as well as those of small concentrations of perchlorate suggest that chaotropic actions can contribute to these effects. The difference between the effects of anionic and cationic agents, as well as between the effects of n-alkanols of different size may be attributable to the different intensity of similar effects at different membrane sites.