Extracellular calcium and the inotropic effect of epinephrine on frog skeletal muscle

The purpose of these experiments was to determine if extracellular calcium plays an important role in mediating the inotropic effect of epinephrine in isolated frog sartorius muscle. Initial experiments indicated that epinephrine potentiated the muscle twitch in a concentration-dependent manner with concentrations of 10 microM to 1 mM, increasing peak tension by approximately 33%. To inhibit the influx of extracellular calcium, muscles were incubated for 20 min in media containing epinephrine in which calcium had been removed and replaced by magnesium or EDTA, or in experimental media containing epinephrine and the calcium channel blockers D-600 or diltiazem (5 microM). Each experimental condition was found to antagonize the effects of epinephrine such that peak twitch tensions were not significantly different from the control. When muscles were returned to normal Ringer's solution containing epinephrine, twitches exhibited progressive potentiation. Muscles were also incubated for 20 min in epinephrine without stimulation. Once stimulation was resumed, twitches were not immediately potentiated but rather gradually increased over time. These results suggest that the inotropic effects of epinephrine are influenced by the influx of extracellular calcium, an event that is dependent on muscle activation.