Effect of alpha- and beta-sympathomimetic agonists on calcium-dependent slow action potential and force of contraction in the rabbit papillary muscle.

Abstract

The influence of sympathomimetic α- and β-agonists on calcium-dependent slow action potential (SAP) and force of contraction were analyzed in the partially depolarized rabbit papillary muscle. 1. The effects of phenylephrine (3×10−6 mol/l) on SAP were compared with those of isoprenaline (5×10−8 mol/l) since the contractions that could be elicited at these concentrations were of similar amplitude. The maximum rate of rise (Vmax) of the slow action potential, which was taken to reflect the slow calcium inward current (Isi), was evidently smaller when elicited by phenylephrine than by isoprenaline. 2. Vmax of SAP induced by phenylephrine (3×10−6 mol/l) or isoprenaline (5×10−8 mol/l) was significantly increased in either case by additional application of isoprenaline. The positive inotropic effect induced by additional isoprenaline was associated with an increase in the rate of force development. 3. Vmax of SAP evoked by isoprenaline (5×10−8 mol/l) remained unchanged by additional application of phenylephrine (3×10−6 mol/l) whereas the duration of SAP was significantly prolonged. Additional phenylephrine markedly increased the time to peak force but left the rate of force development unchanged. These effects of phenylephrine on slow action potential and force of contraction were completely blocked by prazosin (10−8 mol/l). 4. The duration of SAP induced by dopamine was shortened by prazosin (10−8 mol/l) without alteration of Vmax, whereas force of contraction was reduced. 5. For further analysis of the mechanisms responsible for the prolongation of SAP by the α-mimetic effect of phenylephrine, additional experiments have been performed. In normal Tyrode solution containing MnCl2 (10 mmol/l), phenylephrine (3×10−6 mol/l) prolonged the duration of action potential without reestablishing force development. Prazosin (10−8 mol/l) completely antagonized this effect of phenylephrine. 6. These findings indicate that an increase in the slow calcium inward current induced by α-stimulation is much smaller than that induced by β-stimulation. The prolongation of the action potential evoked by α-stimulation seems to be induced by a suppression of the time-dependent outward current. This current may play an important role in the α-adrenoceptor-mediated positive inotropic effect.