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Am J Physiol Heart Circ Physiol 279: H1329-H1337, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 3, H1329-H1337, September 2000

Conditioning of beta 1-adrenoceptor effect via beta 2-subtype on L-type Ca2+ current in canine ventricular myocytes

Zsolt Nagykaldi1, David Kem1,3, Ralph Lazzara2,3, and Bela Szabo2,3

1 Sections of Endocrinology and 2 Cardiology, Department of Internal Medicine, and 3 Cardiac Arrhythmia Research Institute, University of Oklahoma Health Sciences Center and Veterans Affairs Medical Center, Oklahoma City, Oklahoma 73104

We investigated the roles of beta 1- and beta 2-receptors (beta -AR) in adrenergic enhancement of L-type Ca2+ current (ICaL) in canine ventricular myocytes. Isoproterenol and l-norepinephrine produced a monophasic and a biphasic concentration-ICaL relationship (CR), respectively. alpha 1-AR inhibition with prazosin and beta 2-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 ICaL. beta 2-AR inhibition with ICI-118551 reduced the Emax 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 ICaL response to beta 1-AR stimulation but abolished the enhancement via beta 2-AR. Zinterol augmented the enhancement of ICaL by forskolin, IBMX, and theophylline, but not in the presence of CGP-20712A. We conclude that selective beta 2-AR stimulation does not increase ICaL but enhances adenylyl cyclase activity when stimulated via beta 1-AR and with forskolin. beta 2-AR activity preconditions adenylyl cyclase for beta 1-AR stimulation.

norepinephrine; carbachol; 3-isobutyl-1-methylxanthine; adenylyl cyclase; forskolin


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[Abstract] [Full Text]


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