AJP - Heart and Circulatory Physiology, Vol 266, Issue 6 2310-H2319, Copyright © 1994 by American Physiological Society
Beta-adrenergic regulation of action potentials and automaticity in young and adult canine purkinje fibers
F. Charpentier and M. R. Rosen
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
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.
