[The coupling of canine ventricular myocyte beta2-adrenoceptors to L-type calcium current].
To establish the functional coupling of beta adrenoceptor (beta AR) subtypes of beta 1AR and beta 2AR to L-type calcium current (ICaL), we investigated the non-selective agonist isoproterenol (ISO), and the relatively selective beta 2AR agonists zinterol (ZIN) and salbutamol (SAL) on ICaL in isolated canine ventricular myocytes in the presence and absence of CGP 20712A (CGP) and atenolol (AT), selective beta 1AR antagonists, and ICI 118,551 (ICI) a selective beta 2AR antagonist. Peak ICaL was determined using "patch type" microelectrodes and whole cell voltage clamp. ISO (0.5 microM) increased ICaL maximally 3.5 +/- 0.67 fold. ZIN (10.0 microM) and SAL (10.0 microM) increased ICaL maximally 1.5 +/- 0.2 (n = 5) fold and 1.4 +/- 0.1 (n = 5) fold, respectively. These effects were fully inhibited by CGP (0.3 microM) and AT (1.0 microM), inhibitors of beta 1AR but not by ICI (0.1 microM) a beta 2AR inhibitor. ZIN at relatively lower concentrations (< or = 0.1 microM) did not increase ICaL. CGP (0.3 microM) but not AT and ICI inhibited ICaL in the absence of beta AR agonists. CGP inhibition of ICaL was absent in the presence of forskolin (FK, 1.0 microM) that increases cAMP levels and ICaL by directly stimulating the adenylate cyclase. These indicate that none of the antagonists affect ICaL through an action downstream of beta AR.


CONCLUSIONS
beta-adrenergic agonists increase ICaL via beta 1AR but not beta 2AR in canine ventricular myocytes.
Nagykáldi
Z
Z
Department of Internal Medicine, University of Oklahoma HSC, Oklahoma City, USA.
Kem
D
D
Lazzara
R
R
Szabó
B
B
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D004983:Ethanolamines; D007093:Imidazoles; D018343:Receptors, Adrenergic, beta-2; D005576:Colforsin; D001262:Atenolol; C002904:zinterol; C049763:CGP 20712A; D000242:Cyclic AMP; D000420:Albuterol