Do beta 2-adrenergic receptors modulate Ca2+ in adult rat ventricular myocytes?
We examined the role of beta 2-adrenergic receptors (ARs) in modulating calcium homeostasis in rat ventricular myocytes. Zinterol (10 microM), an agonist with a 25-fold greater affinity for beta 2-ARs over beta 1-ARs, modestly enhanced L-type calcium current (ICa) magnitude by approximately 30% and modestly accelerated the rate of Ca2+ concentration ([Ca2+]) decline (approximately 35%) but had little effect on the magnitude of the [Ca2+] transient (a nonsignificant 6% increase). However, 1 microM of the highly selective beta 1-AR antagonist CGP-20712A completely blocked the ICa increase induced by 10 microM zinterol. Pretreatment of cells with pertussis toxin (PTX) did not alter ICa enhancement by 10 microM zinterol, although it did abolish the ability of acetylcholine to block the forskolin-induced enhancement of ICa. Zinterol (10 microM) approximately doubled adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, although one-half of this increase was blocked by CGP-20712A. In contrast, 1 microM of the nonselective beta-agonist isoproterenol increased cAMP production 15-fold. Thus we found no evidence that activation of beta 2-ARs modulates calcium homeostasis in rat ventricular myocytes, even after treatment with PTX.
Laflamme
M A
MA
Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Becker
P L
PL
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004553:Electric Conductivity; D004983:Ethanolamines / Q000494:pharmacology; D006352:Heart Ventricles; D006706:Homeostasis / Q000187:drug effects; D007425:Intracellular Membranes / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; C002904:zinterol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D002118:Calcium