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

Abstract

Reported effects of α-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 ( I ti) responsible for OAP. The I ti was induced in isolated rabbit Purkinje fibers either by acetylstrophanthidin or 8 m m Ca. The magnitude of the I ti was determined at various membrane potentials after activation by steps to −10 mV from a holding potential of −80 mV. When the I ti was induced by acetylstrophanthidin, phenylephrine (10 −7 to 10 −5 m) caused inhibition of I ti at all potentials tested. Phenylephrine also caused a significant decrease in net outward current at plateau voltages. Both effects were blocked by prazosin (5 × 10 −7 m) but not by propranolol (5 × 10 −7 m). Prazosin also strongly inhibited the I ti in the absence of phenylephrine. At 5 × 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 I ti was induced by 8 m m Ca, the effect of phenylephrine, but not prazosin, reversed so that phenylephrine increased the amplitude of the I ti. Thus, α-adrenergic agonists may exert either inhibitory or stimulatory effects on the I ti 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 suppres OAP by an action on the I ti which is independent of α-adrenergic or local anaesthetic actions.