Adrenergic prolongation of action potential duration in rainbow trout myocardium via inhibition of the delayed rectifier potassium current, IKr

Catecholamines mediate the 'fight or flight' response in a wide variety of vertebrates. The endogenous cate-cholamine adrenaline increases heart rate and contractile strength to raise cardiac output. The increase in contractile force is driven in large part by an increase in myocyte Ca2+ influx on the L-type Ca current (I-CaL) during the cardiac action potential (AP). Here, we report a K+- based mechanism that prolongs AP duration (APD) in fish hearts following adrenergic stimulation. We show that adrenergic stimulation inhibits the delayed rectifier K+ current (I-Kr) in rainbow trout (Oncorhynchus mykiss) cardiomyocytes. This slows repolarization and prolongs APD which may contribute to positive inotropy following adrenergic stimulation in fish hearts. The endogenous ligand, adrenaline (1 mu M), which activates both alpha-and beta-ARs reduced maximal IKr tail current to 61.4 +/- 3.9% of control in atrial and ventricular myocytes resulting in an APD prolongation of similar to 20% at both 50 and 90% repolarization. This effect was reproduced by the alpha-specific adrenergic agonist, phenylephrine (1 mu M), but not the beta-specific adrenergic agonist isoproterenol (1 mu M). Adrenaline (1 mu M) in the presence of beta(1) and beta(2)- blockers (1 mu M atenolol and 1 mu M ICI-118551, respectively) also inhibited I-Kr. Thus, I-Kr suppression following alpha-adrenergic stimulation leads to APD prolongation in the rainbow trout heart. This is the first time this mechanism has been identified in fish and may act in unison with the well-known enhancement of I-CaL following adrenergic stimulation to prolong APD and increase cardiac inotropy.