Modulation of the cardiac transient outward current by catecholamines.

We studied modulation of the transient outward current in single canine Purkinje cells that were voltage clamped under Ca2+-free conditions using the patch pipette. The current showed two exponential time constants of inactivation (48, 352 ms at +58 mV and 53, 325 ms at +78 mV). Norepinephrine or isoproterenol 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 or isoproterenol reduced the amplitude of the fast time constant component of inactivation, while increasing the amplitude of the slow component, without changing their time constants. They 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. Intracellular perfusion with the catalytic subunit of the cAMP-activated protein kinase reproduced the modulation of the current. These results suggest a role for neurotransmitter regulation of the transient outward current in cardiac cells, perhaps by channel phosphorylation.