Electrophysiological characterization of cardiac beta 2-adrenoceptors in sheep Purkinje fibers.
The electrophysiological effects mediated by beta 2-adrenoceptor stimulation were studied in sheep cardiac Purkinje fibers. beta 2-Adrenoceptor stimulation was achieved by using isoproterenol (ISO) in the presence of the highly selective beta 1-antagonist CGP 20712A. ICI 118,551 was used as a selective beta 2-antagonist. In driven preparations, ISO (0.1 to 1 microM) caused a positive inotropic effect which was associated with the shortening of action potential duration and was completely abolished only by the simultaneous presence of CGP 20712A (0.3 microM) and ICI 118,551 (50 nM). In previously quiescent preparations, ISO (0.1 to 1 microM) induced spontaneous activity in 15 out of 24 preparations. In the presence of CGP 20712A (0.3 microM) only five preparations out of 24 became automatic when exposed to ISO, and their rate of firing was significantly reduced (13 +/- 4 vs. 43 +/- 6 beats/min, P less than 0.05) with respect to ISO alone. CGP 20712A completely abolished the steepening of diastolic depolarization and the increase of the pacemaker current caused by ISO (0.1 to 1 microM). The beta 2-antagonist ICI 118,551 (50 nM) completely failed to modify the effect of ISO on the rate of spontaneous firing, the slope of diastolic depolarization and the pacemaker current. On the other hand, the increase of oscillatory afterpotential (OAP) amplitude caused by ISO in strophanthidin-treated preparations was significantly reduced only by the beta 1-antagonist CGP 20712A, but not by the beta 2-antagonist ICI 118,551. These results demonstrate that beta 2-adrenoceptors are functionally present in sheep Purkinje fibers where their stimulation consistently causes a positive inotropic effect. However, beta 2-adrenoceptors do not appear to affect the processes of normal automaticity, and do not greatly contribute to triggered activity due to OAPs.
Cerbai
E
E
Department of Pharmacology, University of Firenze, Italy.
Masini
I
I
Mugelli
A
A
D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012756:Sheep / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; C049763:CGP 20712A; D007545:Isoproterenol