Canine Ventricular Myocyte β2‐Adrenoceptors Are Not Functionally Coupled to L‐Type Calcium Current

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Abstract
Selective Stimulation of β AR Subtypes and ICaL.Introduction: To establish the functional coupling of beta adrenoceptor (βAR) subtypes β1, AR and β2AR to L‐type calcium current (ICaL)we investigated the nonselective agonist isoproterenol (ISO) and the relatively selective β1AR antagonists zinterol (ZIN) and salbutamol (SAL) on ICaLin isolated canine ventricular myocytes in the presence and absence of CGP 20712A (CGP) and atenolol (AT), selective β1AR antagonists, and ICI 118,551 (ICI) a selective β2AR antagonist.Methods and Results: Peak ICaLdetermined using “patch type” microelectrodes and whole cell voltage clamp. ISO (0.5 μM) increased ICaL, maximally 3.5 ± 0.67 fold. ZIN (10.0 μM) and SAL (10.0 μM) increased ICaLmaximally 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 β1AR, but not by ICI (0.1 μM), which is a β2AR inhibitor. ZIN at relatively lower concentrations (≤0.1 μM) did not increase ICaL. CGP (0.3 μM) but not AT and ICI inhibited ICaLin the absence of βAR agonists. CGP inhibition of ICaL, was absent in the presence of forskolin (1.0 μM), which increases cAMP levels and ICaLby directly stimulating the adenylate cyclase. These data indicate that none of the antagonists affect ICaLthrough an action downstream βAR.Conclusion: β‐Adrenergic agonists increase ICaLvia β1AR but not β2AR in canine ventricular myocytes.