Conditioning of β1-adrenoceptor effect via β2-subtype on L-type Ca2+ current in canine ventricular myocytes

Abstract

We investigated the roles of β1- and β2-receptors (β-AR) in adrenergic enhancement of L-type Ca2+ current ( I CaL) in canine ventricular myocytes. Isoproterenol and l-norepinephrine produced a monophasic and a biphasic concentration- I CaL relationship (CR), respectively. α1-AR inhibition with prazosin and β2-AR stimulation with zinterol or l-epinephrine shifted the CR of l-norepinephrine leftward. Zinterol (50 nM) and l-epinephrine (10 nM), but not prazosin, altered the biphasic CR of l-norepinephrine to a monophasic CR. Zinterol and l-epinephrine applied after l-norepinephrine had no effect on I CaL. β2-AR inhibition with ICI-118551 reduced the E max of isoproterenol and l-norepinephrine by 60% and abolished the augmentation of l-norepinephrine by zinterol and l-epinephrine. Carbachol (100 nM) modestly reduced the I CaLresponse to β1-AR stimulation but abolished the enhancement via β2-AR. Zinterol augmented the enhancement of I CaL by forskolin, IBMX, and theophylline, but not in the presence of CGP-20712A. We conclude that selective β2-AR stimulation does not increase I CaL but enhances adenylyl cyclase activity when stimulated via β1-AR and with forskolin. β2-AR activity preconditions adenylyl cyclase for β1-AR stimulation.