Inhibitory effect mediated by α1-adrenoceptors on transient outward current in isolated rat ventricular cells

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Abstract
In order to clarify the underlying ionic mechanism(s) by whichα 1-adrenoceptor stimulation prolongs the action potential duration (APD), single rat ventricular cells were voltage-clamped under a Na+-free condition using patch pipettes. Depolarizing pulses from a holding potential of -77 mV induced a 4-aminopyridine-sensitive transient outward current (Ito). Phenylephrine, in the presence of theβ-blocker propranolol (1μM), inhibited Ito in a concentration-dependent fashion and the maximum inhibition of Ito (42.5±10.0%, n=5) was produced by 30μM phenylephrine. The inhibitory effect of phenylephrine on Ito was almost abolished by 1μM. prazosin, a selectiveα 1-blocker, indicating that the Ito inhibition is mediated byα 1-adrenoceptors. On the other hand, phenylephrine had little influence on the Ca2+ current in the presence of 4-aminopyridine. In isolated rat papillary muscles, both theα 1-adrenoceptor-mediated APD prolongation and positive inotropic response were markedly attenuated by pretreatment with 1.5 mM 4-aminopyridine. These results suggest that the inhibition of Ito is a primary cause of the prolongation of APD produced byα 1-adrenoceptor stimulation and that the Ito inhibition may be causally related to the positive inotropic effect mediated byα 1-adrenoceptors.

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