Do β2-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 mu M), an agonist with a 25-fold greater affinity for beta(2)-ARs over beta(1)-ARs, modestly enhanced L-type calcium current (I-Ca) magnitude by similar to 30% and modestly accelerated the rate of Ca2+ concentration ([Ca2+]) decline (similar to 35%) but had little effect on the magnitude of the [Ca2+] transient (a nonsignificant 6% increase). However, 1 mu M of the highly selective beta(1)-AR antagonist CGP-20712A completely blocked the I-Ca increase induced by 10 mu M zinterol. Pretreatment of cells with pertussis toxin (PTX) did not alter I-Ca enhancement by 10 mu M zinterol, although it did abolish the ability of acetylcholine to block the forskolin-induced enhancement of I-Ca. Zinterol (10 mu M) approximately doubled adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, although one-half of this increase was blocked by CGP-20712A. In contrast, 1 mu M 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.