Canine Ventricular Myocyte β 2 ‐Adrenoceptors Are Not Functionally Coupled to L‐Type Calcium Current

Selective Stimulation of β AR Subtypes and I CaL . Introduction : To establish the functional coupling of beta adrenoceptor (βAR) subtypes β 1 , AR and β 2 AR to L‐type calcium current (I CaL )we investigated the nonselective agonist isoproterenol (ISO) and the relatively selective β 1 AR antagonists zinterol (ZIN) and salbutamol (SAL) on I CaL in isolated canine ventricular myocytes in the presence and absence of CGP 20712A (CGP) and atenolol (AT), selective β 1 AR antagonists, and ICI 118,551 (ICI) a selective β 2 AR antagonist. Methods and Results : Peak I CaL determined using “patch type” microelectrodes and whole cell voltage clamp. ISO (0.5 μM) increased I CaL , maximally 3.5 ± 0.67 fold. ZIN (10.0 μM) and SAL (10.0 μM) increased I CaL maximally 1.5 ± 0.2 fold (n = 5) and 1.4 ± 0.1 fold (n = 5) respectively. These effects were fully inhibited by CGP (0.3 μM) and AT (1.0 μM), which are inhibitors of β 1 AR, but not by ICI (0.1 μM), which is a β 2 AR inhibitor. ZIN at relatively lower concentrations (≤0.1 μM) did not increase I CaL . CGP (0.3 μM) but not AT and ICI inhibited I CaL in the absence of βAR agonists. CGP inhibition of I CaL , was absent in the presence of forskolin (1.0 μM), which increases cAMP levels and I CaL by directly stimulating the adenylate cyclase. These data indicate that none of the antagonists affect I CaL through an action downstream βAR. Conclusion : β‐Adrenergic agonists increase I CaL via β 1 AR but not β 2 AR in canine ventricular myocytes.