Antagonistic Action of α-and β-Agonists on the Bullfrog Atrium

Action of α-and β-agonists on the membrane potential, current and tension components on the bullfrog atrial muscle were studied by means of the single or double sucrose-gap technique. Isoproterenol (10-9-10-5M) as well as adrenaline (10-7-10-4M) produced a dose-dependent positive inotropic effect, while methoxamine (10-8-10-4M) and phenylephrine (10-8-10-3M) with propranolol (10-6M) elicited a negative inotropic effect. The positive inotropic effect was accompanied by slight hyperpolarization and marked increase of overshoot and plateau level of action potential, and the negative inotropic effect, by opposite changes. Under voltage clamp, isoproterenol and adrenaline produced enhancement of slow inward current (Is), delayed outward current (Ix) and Is-dependent phasic tension, while Is-independent tonic tension was inhibited. Contrarily, methoxamine and phenylephrine depressed these currents and elicited β-antagonistic inotropic actions, especially when isoproterenol was present. Specific feature of α-agonist action in the presence of isoproterenol was an inward shift of the semi-steady I-V relationship. It is thus suggested that, in the bullfrog atrium, α-agonists produce a strong β-receptor blocking action and an inward shift of the background current. A possible relationship between the latter effect and inhibition of the Na-K pump is also suggested.