Effects of alpha-adrenergic agents on transient inward current in rabbit Purkinje fibers

Reported effects of alpha-adrenergic agents on oscillatory afterpotentials (OAP) are conflicting. Therefore, we used standard two microelectrode voltage clamp techniques to determine the effects of phenylephrine and prazosin on the transient inward current (Iti) responsible for OAP. The Iti was induced in isolated rabbit Purkinje fibers either by acetylstrophanthidin or 8 mM Ca. The magnitude of the Iti was determined at various membrane potentials after activation by steps to -10 mV from a holding potential of -80 mV. When the Iti was induced by acetylstrophanthidin, phenylephrine (10(-7) to 10(-5)M) caused inhibition of Iti at all potentials tested. Phenylephrine also caused a significant decrease in net outward current at plateau voltages. Both effects were blocked by prazosin (5 x 10(-7)M) but not by propranolol (5 x 10(-7)M). Prazosin also strongly inhibited the Iti in the absence of phenylephrine. At 5 x 10(-7)M, prazosin did not affect sodium current activated by voltage steps from -80 to -45 mV or maximum upstroke velocity during interruptions of the voltage clamp. When the Iti was induced by 8 mM Ca, the effect of phenylephrine, but not prazosin, reversed so that phenylephrine increased the amplitude of the Iti. Thus, alpha-adrenergic agonists may exert either inhibitory or stimulatory effects on the Iti depending on the mechanism by which the current is induced. Additional effects on OAP amplitude may be induced by changes in action potential duration mediated through actions on net outward current. Prazosin may suppress OAP by an action on the Iti which is independent of alpha-adrenergic or local anaesthetic actions.