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Journal of Pharmacology And Experimental Therapeutics, Vol. 191, Issue 1, 109-118, 1974
Copyright © 1974 by American Society for Pharmacology and Experimental Therapeutics

REACTIVITY OF CHICK EMBRYO HEART TO CHOLINERGIC AGONISTS DURING ONTOGENESIS: DECLINE IN DESENSITIZATION AT THE ONSET OF CHOLINERGIC TRANSMISSION

Achilles J. Pappano 1 and Carol A. Skowronek 1

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

Acetylcholine, acetyl-beta-methylcholine and carbamylcholine inhibited sinoatrial pacemaker activity in atria isolated from chick embryos on the 6th, 12th and 18th incubation days. Cardioinhibition persisted throughout the 5-minute exposure to cholinergic agonists in sinoatrial preparations from the 12th and l8th incubation days whereas automaticity recovered completely within 1 to 2 minutes in preparations from the 6th incubation day. Neither hydrolysis by acetylcholinesterase nor release of catecholamines from cardiac stores accounted adequately for the brevity of pacemaker inhibition by choline esters on the 6th incubation day. Evidence suggested that desensitization, most prominently observed with carbamylcholine, restricted the duration of cholinergic inhibition of the pacemaker on the 6th incubation day. Although automaticity recovered completely within 2 minutes after initial application of acetylcholine and carbamylcholine, pacemaker cells were not inhibited by a second application until the tissues had been bathed in drug-free saline for 10 to 20 minutes. The decline in desensitization may be due to developmental changes in the atropine-sensitive cholinergic receptor and/or in the potassium conductance activatd by the drug-receptor interaction. The ontogenetic decline in desensitization occurred around the time that cholinergic transmission to the sinoatrial pacemaker appeared (12th incubation day) and reactivity of the pacemaker to cholinergic agonists increased. Like skeletal muscle, chick embryo atria underwent a change in reactivity to tetrodotoxin and to cholinergic agonists at the time of cholinergic innervation.

Submitted on January 14, 1974
Accepted on May 30, 1974




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L. A. McKinnon and N. M. Nathanson
Tissue-specific Regulation of Muscarinic Acetylcholine Receptor Expression during Embryonic Development
J. Biol. Chem., September 1, 1995; 270(35): 20636 - 20642.
[Abstract] [Full Text] [PDF]


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