Developmental changes in the effects of nadolol on adult and neonatal canine Purkinje fibers.
We used standard microelectrode techniques to determine developmental differences in the direct membrane and beta-blocking effects of nadolol on the electrophysiologic properties of adult and neonatal canine Purkinje fibers (PF). To study direct membrane effects, we superfused PF with nadolol 1 X 10(-8)-1 X 10(-4) M while stimulating them at a BCL of 800 ms. Nadolol less than 1 X 10(-5) M had no effect on the transmembrane potential in either age group. Nadolol, greater than or equal to 1 X 10(-5) M, increased action potential duration at 100% repolarization (APD100) in adult fibers and nadolol, 1 X 10(-4) M, decreased Vmax and APD at 50% repolarization (APD50) in neonatal fibers (p less than 0.05). The beta-blocking effects of nadolol were studied by examining the chronotropic response in automatic PF to cumulative doses of l-isoproterenol.HCl 3 X 10(-10)-3 X 10(-6) M, alone and then in the continued presence of nadolol 5 X 10(-8)-5 X 10(-6) M. Nadolol caused a concentration-dependent shift to the right of the concentration-response curve in both age groups. pA2 determinations in adult (7.88) and neonatal (7.57) PF indicated that there was no developmental difference in the affinity of nadolol for the beta-receptor (p greater than 0.05). Our results indicate that nadolol shows developmental changes in its direct membrane effects but not its beta-blocking effects. The latter characteristic differs from that of the more highly lipid-soluble beta-blocker, propranolol. This suggests that different beta-blocking molecules have differing abilities to block the beta-receptor at different ages that are influenced importantly by their lipid solubility.
Hamra
M
M
Division of Developmental Pharmacology, College of Physicians and Surgeons of Columbia University, New York, N.Y.
Danilo
P
P
Rosen
M R
MR
D000200:Action Potentials / Q000187:drug effects; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009248:Nadolol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D012995:Solubility
D009248:Nadolol; D011433:Propranolol