F. Charpentier et Mr. Rosen, BETA-ADRENERGIC REGULATION OF ACTION-POTENTIALS AND AUTOMATICITY IN YOUNG AND ADULT CANINE PURKINJE-FIBERS, The American journal of physiology, 266(6), 1994, pp. 80002310-80002319
To investigate developmental changes in the cellular electrophysiologi
cal effects of beta(1)- and beta(2)-adrenoceptor stimulation on canine
Purkinje fibers (PF), we studied the effects of isoproterenol, a nons
elective beta-agonist, and salbutamol, a preponderantly beta(2)-agonis
t, alone or in presence of the selective beta(1)-antagonist CGP-20712A
or the beta(2)-antagonist ICI-118551. Standard microelectrode techniq
ues were used to study adult and neonatal (<11 days) PF paced at a cyc
le 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 (APD(60) and APD(90)) in a concentration-dependen
t fashion. These effects were not observed in neonatal PF, which inste
ad manifested a significant increase in phase 2 amplitude and APD(30)
that was not observed in adult PF. All these effects occurred as well
with salbutamol but were less pronounced and required higher agonist c
oncentrations. Isoproterenol decreased the automatic cycle length of a
dult fibers from 4,079 +/- 796 ms during controlto 2,190 +/- 229 ms at
10(-5) M (P < 0.05) and from 1,535 +/- 105 to 1,249 +/- 90 ms in neon
atal 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 ef
fect 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-2071
2A significantly antagonized them. In conclusion, 1) the effects of be
ta-adrenergic stimulation on transmembrane potentials of canine PF cha
nge during development, both qualitatively (in paced PF) and quantitat
ively (in automatic PF) and 2) the responses seen are attributable to
the activation of beta(1)- and not beta(2)-adrenoceptors.