Norepinephrine and alpha-adrenoceptor agonists strongly inhibit the transient outward K+ current in rabbit and human atria, substantially slowing action potential repolarization.
In the heart, alpha-adrenergic agonists have long been known to produce a positive inotropic effect that is rate dependent and associated with action potential prolongation but is not accompanied by adenosine 3',5'-cyclic monophosphate (cAMP) elevation. The ionic mechanism of these effects is unknown. We report that a transient outward K+ current, a major determinant of plateau duration in rabbit and human atria, is strongly inhibited by norepinephrine and the alpha-adrenoceptor agonists methoxamine and phenylephrine. These effects of alpha-stimulation can be blocked by prazosin. The reduction in the transient outward current substantially slows action potential repolarization. These results can explain the regional and species-dependent positive inotropic effects of alpha-adrenergic stimulation in the heart and give important new insight into the autonomic regulation of cardiac function. In addition, reduction in this repolarizing current during the enhanced alpha-adrenergic responsiveness of myocardial ischemia may be a factor in the genesis of arrhythmias produced by catecholamines.
Fedida et al. (Mon,) conducted a other in Cardiac electrophysiology. Norepinephrine and alpha-adrenoceptor agonists (methoxamine, phenylephrine) vs. Prazosin (blockade) was evaluated on Transient outward K+ current and action potential repolarization. Norepinephrine and alpha-adrenoceptor agonists strongly inhibit the transient outward K+ current in rabbit and human atria, substantially slowing action potential repolarization.
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