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Journal of Pharmacology And Experimental Therapeutics, Vol. 191, Issue 3, 479-486, 1974
Copyright © 1974 by American Society for Pharmacology and Experimental Therapeutics

INCREASED SENSITIVITY OF SINOATRIAL PACEMAKER TO ACETYLCHOLINE AND TO CATECHOLAMINES AT THE ONSET OF AUTONOMIC NEUROEFFECTOR TRANSMISSION IN CHICK EMBRYO HEART

Konrad Löffelholz 1 and Achilles J. Pappano 1

1 Department of Pharmacology, University of Connecticut Health Center, Farmington, Connecticut

The inhibitory effects of acetylcholine (ACh) and the acceleratory effects of epinephrine (EPI) and isoproterenol (ISO) on pacemaker activity were studied in isolated sinoatrial preparations of the chick embryo heart. Sensitivity of the pacemaker to ACh increased significantly between the 9th and 11th incubation days whereas it did not change between the 6th and 9th and between the 11th and 18th incubation days. Increased sensitivity to ACh occurred just prior to the initial appearance of cholinergic neuroeffector transmission on the 12th incubation day and contributed, at least in part, to the development of cholinergic transmission. Pacemaker sensitivity to EPI and ISO was high on the 18th incubation day, decreased on the 19th and 20th incubation days, and then increased on the 21st incubation day to equal that of the 18th incubation day. Increased sensitivity to catecholamines on the 21st incubation day coincided with the appearance of adrenergic neuroeffector transmission and may be related to an effect of functional innervation and/or to the removal of a depressant mechanism associated with ontogenesis. Operation of a neuronal transport mechanism did not adequately account for the reduction in adrenergic sensitivity on the 2 days prior to hatching because the sensitivity to ISO decreased significantly as did that to EPI. A change in cardiac responsiveness produced by hypoxia seen late in ontogenesis could be responsible provided the cellular alteration persisted in vitro. Alternatively, increased metabolism by catechol-O-methyltransferase, whose reported activity increased at the same time that adrenergic sensitivity decreased, may account for the phenomenon.

Submitted on November 24, 1974
Accepted on July 12, 1974




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Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics.