Canine ventricular myocyte beta2-adrenoceptors are not functionally coupled to L-type calcium current.
BACKGROUND
To establish the functional coupling of beta adrenoceptor (betaAR) subtypes beta1AR and beta2AR to L-type calcium current (I(CaL)), we investigated the nonselective agonist isoproterenol (ISO) and the relatively selective beta2AR agonists 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 beta1AR antagonists, and ICI 118,551 (ICI) a selective beta2AR antagonist.


RESULTS
Peak I(CaL) was determined using "patch type" microelectrodes and whole cell voltage clamp. ISO (0.5 microM) increased I(CaL) maximally 3.5 +/- 0.67 fold. ZIN (10.0 microM) and SAL (10.0 microM) 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 microM) and AT (1.0 microM), which are inhibitors of beta1AR, but not by ICI (0.1 microM), which is a beta2AR inhibitor. ZIN at relatively lower concentrations (< or = 0.1 microM) did not increase I(CaL). CGP (0.3 microM) but not AT and ICI inhibited I(CaL) in the absence of betaAR agonists. CGP inhibition of I(CaL) was absent in the presence of forskolin (1.0 microM), 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 of betaAR.


CONCLUSIONS
Beta-adrenergic agonists increase I(CaL) via beta1AR but not beta2AR in canine ventricular myocytes.
Nagykaldi
Z
Z
Department of Internal Medicine, University of Oklahoma Health Sciences Center and the Veterans Administration Medical Center, Oklahoma City, USA.
Kem
D
D
Lazzara
R
R
Szabo
B
B
D000818:Animals; D002118:Calcium / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004285:Dogs; D017136:Ion Transport / Q000502:physiology; D018408:Patch-Clamp Techniques; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D016276:Ventricular Function
D020746:Calcium Channels, L-Type; D011943:Receptors, Adrenergic, beta; D002118:Calcium