Do β2-adrenergic receptors modulate Ca2+ in adult rat ventricular myocytes?

Abstract

We examined the role of β2-adrenergic receptors (ARs) in modulating calcium homeostasis in rat ventricular myocytes. Zinterol (10 μM), an agonist with a 25-fold greater affinity for β2-ARs over β1-ARs, modestly enhanced L-type calcium current ( I Ca) magnitude by ∼30% and modestly accelerated the rate of Ca2+ concentration ([Ca2+]) decline (∼35%) but had little effect on the magnitude of the [Ca2+] transient (a nonsignificant 6% increase). However, 1 μM of the highly selective β1-AR antagonist CGP-20712A completely blocked the I Ca increase induced by 10 μM zinterol. Pretreatment of cells with pertussis toxin (PTX) did not alter I Ca enhancement by 10 μM zinterol, although it did abolish the ability of acetylcholine to block the forskolin-induced enhancement of I Ca. Zinterol (10 μM) approximately doubled adenosine 3′,5′-cyclic monophosphate (cAMP) accumulation, although one-half of this increase was blocked by CGP-20712A. In contrast, 1 μM of the nonselective β-agonist isoproterenol increased cAMP production 15-fold. Thus we found no evidence that activation of β2-ARs modulates calcium homeostasis in rat ventricular myocytes, even after treatment with PTX.