Adrenergic modulation of the transient outward current in isolated canine Purkinje cells

Single canine Purkinje cells were voltage clamped under Ca2+-free conditions using the patch pipette. Depolarizing pulses from a holding potential of -42 mV induced a time-dependent rapidly activating-slowly inactivating outward current, which was identified as the transient outward current. The current showed two exponential time constants of inactivation (48,352 msec at +58 mV and 53,325 msec at +78 mV). Norepinephrine in concentrations exceeding 10(-9) M modified the inactivation kinetics of this current without affecting the activation kinetics. The half-maximum dose for norepinephrine effect was 1.9 X 10(-8) M, and the effect was saturated at 10(-6) M. Norepinephrine reduced the amplitude of the fast time constant component of inactivation, while increasing the amplitude of the slow component, without changing their time constants. Norepinephrine also increased the amplitude of a time-independent current component. The beta-antagonist sotalol blocked the norepinephrine effect on the transient outward current. On the other hand, both activation of adenyl cyclase by forskolin and increase of intracellular cAMP concentration produced the same effect as exposure to norepinephrine. These results suggest a role for neurotransmitter regulation of the transient outward current in cardiac cells, perhaps by channel phosphorylation.