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Determination of transmitter function by neuronal activity

Walicke, Patricia A. and Campenot, Robert B. and Patterson, Paul H. (1977) Determination of transmitter function by neuronal activity. Proceedings of the National Academy of Sciences of the United States of America, 74 (12). pp. 5767-5771. ISSN 0027-8424. PMCID PMC431875.

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The role of neuronal activity in the determination of transmitter function was studied in cultures of dissociated sympathetic neurons from newborn rat superior cervical ganglia. Cholinergic and adrenergic differentiation were assayed by incubating the cultures with radioactive choline and tyrosine and determining the rate of synthesis and accumulation of labelled acetylcholine and catecholamines. As in previous studies, pure neuronal cultures grown in control medium displayed much lower ratios of acetylcholine synthesis to catecholamine synthesis than did sister cultures grown in medium previously conditioned by incubation on appropriate nonneuronal cells (conditioned medium). However, here we report that neurons treated with the depolarizing agents elevated K+ or veratridine, or stimulated directly with electrical current, either before or during application of conditioned medium, displayed up to 300-fold lower acetylcholine/catecholamine ratios than they would have without depolarization, and thus remained primarily adrenergic. Elevated K+ and veratridine produced this effect on cholinergic differentiation without significantly altering neuronal survival. Because depolarization causes Ca2+ entry in a number of cell types, the effects of several Ca2+ agonists and antagonists were investigated. In the presence of the Ca2+ antagonists D600 or Mg2+, K+ did not prevent the induction of cholinergic properties by conditioned medium. Thus depolarization, either steady or accompanying activity, is one of the factors determining whether cultured sympathetic neurons become adrenergic or cholinergic, and this effect may be mediated by Ca2+.

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Additional Information:Copyright © 1977 by the National Academy of Sciences. Communicated by David H. Hubel, October 6, 1977. It is a pleasure to acknowledge the excellent assistance of Doreen McDowell and Karen Fischer with the culturing. This work was supported by a grant-in-aid from the American and Massachusetts Heart Associations and a U.S. Public Health Service Grant from the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). P.A.W. is a U.S. Public Health Service Trainee, R.B.C. is a U.S. Public Health Service Postdoctoral Fellow, and P.H.P. is a Career Development Awardee of the NINCDS. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.
Funding AgencyGrant Number
American Heart AssociationUNSPECIFIED
Massachusetts Heart AssociationUNSPECIFIED
National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)UNSPECIFIED
U.S. Public Health Service (USPHS)UNSPECIFIED
Subject Keywords:sympathetic neurons; cell culture; catecholamines; acetylcholine; development
Issue or Number:12
PubMed Central ID:PMC431875
Record Number:CaltechAUTHORS:WALpnas77
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1588
Deposited By: Tony Diaz
Deposited On:01 Feb 2006
Last Modified:02 Oct 2019 22:44

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