Beta-adrenergic regulation of action potentials and automaticity in young and adult canine purkinje fibers.
To investigate developmental changes in the cellular electrophysiological effects of beta 1- and beta 2-adrenoceptor stimulation on canine Purkinje fibers (PF), we studied the effects of isoproterenol, a nonselective beta-agonist, and salbutamol, a preponderantly beta 2-agonist, alone or in presence of the selective beta 1-antagonist CGP-20712A or the beta 2-antagonist ICI-118551. Standard microelectrode techniques were used to study adult and neonatal (< 11 days) PF paced at a cycle length of 1 s or allowed to beat spontaneously. In paced adult PF, isoproterenol significantly increased the maximum diastolic potential and significantly decreased action potential duration at 60 and 90% of full repolarization (APD60 and APD90) in a concentration-dependent fashion. These effects were not observed in neonatal PF, which instead manifested a significant increase in phase 2 amplitude and APD30 that was not observed in adult PF. All these effects occurred as well with salbutamol but were less pronounced and required higher agonist concentrations. Isoproterenol decreased the automatic cycle length of adult fibers from 4,079 +/- 796 ms during control to 2,190 +/- 229 ms at 10(-5) M (P < 0.05) and from 1,535 +/- 105 to 1,249 +/- 90 ms in neonatal PF (P < 0.05). In both adults and neonates, > 90% of this effect was reached at a concentration of 10(-8) M. Salbutamol had the same effect but required higher concentrations. In both adults and neonates, the beta 2-antagonist ICI-118551 did not modify any of the effects of isoproterenol and salbutamol, whereas the beta 1-antagonist CGP-20712A significantly antagonized them. In conclusion, 1) the effects of beta-adrenergic stimulation on transmembrane potentials of canine PF change during development, both qualitatively (in paced PF) and quantitatively (in automatic PF) and 2) the responses seen are attributable to the activation of beta 1- and not beta 2-adrenoceptors.
Charpentier
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Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Rosen
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MR
D000200:Action Potentials; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; C049763:CGP 20712A; D007545:Isoproterenol; D000420:Albuterol