Developmental Changes in the Interactions of Cholinergic and β-Adrenergic Agonists on Electrophysiologic Properties of Canine Cardiac Purkinje Fibers

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Abstract
The parasympathetic nervous system attenuates the effects of sympathetic interventions on the hearts of mature animals. Whereas the vagal mediator, acetylcholine (ACh), alone has minor effects on electrophysiologic properties of the ventricular conducting system, in the presence of sympathetic amines, it induces an accentuated antagonism. Because there are developmental changes in both sympathetic and parasympathetic effects on the heart we studied the parasympathetic and sympathetic interaction in isolated neonatal canine Purkinje fibers (PF), and compared the results to those in adult PF. PF were exposed to isoproterenol (Iso) alone (1 x 10-9, 1 x 10-7 and 1 x 10-5 M) to ACh alone (1 x 10-7 or 1 x 10-5 M) and to Iso in the presence of ACh. In adult PF, supervision with Iso, 10-5 M, alone shortened action potential duration to 50% repolarization from a control value of 215 ± 9 to 200 ± 9. ms (p < 0.01). Simultaneous superfusion of adult PF with Iso 10-5 M and Ach 10-5 M decreased the extent of action potential shortening produced by Iso, so that action potential duration to 50% repolarization shortened from a control value of 221 ± 8 to only 214 ± 12 ms (p < 0.01). The response to superfusion with Iso and Ach (10-5 M) differed significantly from that with Iso alone (p < 0.01). In contrast, exposure of neonatal PF to Iso (10-5 M) prolonged action potential duration to 50% repolarization from a control value of 157 ± 7 to 180 ± 5 ms (p < 0.01). No inhibition of the effect of Iso by Ach (10-7 or 10-5 M) was observed in neonatal PF. At neither age did ACh, alone, exert a significant effect. Our data suggest that accentuated antagonism is not present in young animals having an immature autonomic nervous system, but that it occurs subsequent to maturation.