The positive inotropic effect of epinephrine on skeletal muscle: a brief review

Chronic and acute administration of epinephrine or related sympathomimetic agents are typically prescribed for the treatment of clinical disorders such as hypotension, anaphylactic and allergic reactions, and bronchial asthma. In addition to its effects on these infirmaties and on carbohydrate metabolism, epinephrine also exerts a positive inotropic effect on fast-contracting skeletal muscle in a variety of animal species. At present, the precise mechanisms responsible for the inotropic effect are not known. This communication reviews the positive inotropic effects of epinephrine on fast-contracting skeletal muscle and discusses possible mechanisms which might mediate this phenomenon. Epinephrine potentiates muscle twitches via the second messenger, cAMP, secondary to hormone binding to membrane-bound beta-receptors. Cyclic AMP then acts to increase carbohydrate metabolism, alter sodium/potassium exchange, phosphorylate myosin isozymes, and/or alter intracellular calcium exchange. Based on theoretical grounds, the first three mechanisms can be excluded. Therefore, it is tentatively hypothesized that the effect is due to cAMP-enhanced calcium exchange within the muscle fiber and/or to increased influx of extracellular calcium. This notion is consistent with the mechanism of the positive inotropic effects of epinephrine on cardiac tissue. If this hypothesis is correct, it would also suggest a role, at least under some conditions, for extracellular calcium in the process of skeletal muscle excitation-contraction coupling.