Charpentier F, Rosen M R
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Am J Physiol. 1994 Jun;266(6 Pt 2):H2310-9. doi: 10.1152/ajpheart.1994.266.6.H2310.
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.
为了研究β1-和β2-肾上腺素能受体刺激对犬浦肯野纤维(PF)细胞电生理效应的发育变化,我们研究了非选择性β-激动剂异丙肾上腺素和主要为β2-激动剂的沙丁胺醇单独使用或在选择性β1-拮抗剂CGP-20712A或β2-拮抗剂ICI-118551存在时的效应。采用标准微电极技术研究以1秒周期长度起搏或自发搏动的成年和新生(<11天)PF。在成年PF起搏时,异丙肾上腺素以浓度依赖方式显著增加最大舒张电位,并显著缩短复极化至60%和90%时的动作电位持续时间(APD60和APD90)。这些效应在新生PF中未观察到,新生PF反而表现出2期振幅和APD30显著增加,这在成年PF中未观察到。沙丁胺醇也出现了所有这些效应,但不太明显,且需要更高的激动剂浓度。异丙肾上腺素将成年纤维的自动周期长度从对照时的4079±796毫秒降至10-5 M时的2190±229毫秒(P<0.05),新生PF中从1535±105降至1249±90毫秒(P<0.05)。在成年和新生动物中,>90%的这种效应在10-8 M浓度时达到。沙丁胺醇有相同的效应,但需要更高的浓度。在成年和新生动物中,β2-拮抗剂ICI-118551均未改变异丙肾上腺素和沙丁胺醇的任何效应,而β1-拮抗剂CGP-20712A显著拮抗它们。总之,1)β-肾上腺素能刺激对犬PF跨膜电位的效应在发育过程中发生变化,在定性(起搏PF)和定量(自动PF)方面均如此;2)观察到的反应归因于β1-而非β2-肾上腺素能受体的激活。