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Time Course of the Increase in the Myocardial Slow Inward Current after a Photochemically Generated Concentration Jump of Intracellular cAMP

Nargeot, Joel and Nerbonne, Jeanne M. and Engels, Joachim and Lester, Henry A. (1983) Time Course of the Increase in the Myocardial Slow Inward Current after a Photochemically Generated Concentration Jump of Intracellular cAMP. Proceedings of the National Academy of Sciences of the United States of America, 80 (8). pp. 2395-2399. ISSN 0027-8424. PMCID PMC393827.

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Voltage-clamped atrial trabeculae from bullfrog hearts were exposed to membrane-permeant photolyzable o-nitrobenzyl esters of cAMP and cGMP. UV flashes produced intracellular concentration jumps of cAMP or cGMP. With the cAMP derivative, flashes resulted in an increased slow inward current (Isi), producing a broadened action potential. The Isi reached a maximum 10-30 sec after the flash and decreased over the next 60-300 sec. The first increases were observable within 150 msec; this value is an upper limit imposed by the instrumentation. Responses to flashes lasted longer at higher drug concentrations and in the presence of the phosphodiesterase inhibitor papaverine; effects of flashes developed and decreased faster at higher temperature. Although the amplitude of the Isi was increased, its waveform and voltage sensitivity were not affected. Intracellular concentration jumps of cAMP failed to affect the muscarinic K+ conductance. There were no observable effects of cGMP concentration jumps. The data confirm (i) that cAMP regulates the Isi and (ii) that the 5- to 10-sec delay between application of ß-agonists and the onset of positive inotropic effects, observed in previous studies, has been correctly ascribed to events prior to the interaction between cAMP and protein kinase.

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URLURL TypeDescription CentralArticle
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1983 by the National Academy of Sciences Communicated by James Bonner, January 17, 1983 We thank Roger Spencer for assistance in all phases of the experiments and G. N. Gill, F. Strumwasser, D. Trentham, and R. Y. Tsien for helpful discussion. This research was supported by the National Institutes of Health (Research Career Development Award NS-272 to H.A.L. and Grant GM-29836), by the American Heart Association (a Postdoctoral Fellowship to J.M.N.), and by the Fulbright Exchange Program (a Scholarship to J.N.). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact
Funding AgencyGrant Number
NIH Postdoctoral FellowshipNS-272
American Heart AssociationUNSPECIFIED
Fulbright Exchange ProgramUNSPECIFIED
Subject Keywords:calcium channel; voltage clamp; o-nitrobenzyl ester; cGMP; ß-adrenergic agonist
Issue or Number:8
PubMed Central ID:PMC393827
Record Number:CaltechAUTHORS:NARpnas83
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5789
Deposited By: Archive Administrator
Deposited On:02 Nov 2006
Last Modified:02 Oct 2019 23:26

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