Retinal Horizontal Cell Gap Junctional Conductance is Modulated by Dopamine through a Cyclic AMP-Dependent Protein Kinase

The action of many neuromodulators is mediated by intracellular second messengers such as cyclic AMP. In the retina, exogenously applied dopamine alters the conductance of gap junctions between cultured horizontal cells and this effect is mediated by cyclic AMP. However, it is not known how cyclic A...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1987-10, Vol.84 (20), p.7319-7323
Main Author: Lasater, Eric M.
Format: Article
Language:English
Subjects:
Animals
Bass
Biological and medical sciences
Cell Communication - drug effects
Cell culture techniques
Cell physiology
Connexins
Cultured cells
Cyclic AMP - physiology
Dopamine - pharmacology
Electric current
Electrodes
Fundamental and applied biological sciences. Psychology
Gap junctions
horizontal cells
Intercellular Junctions - drug effects
membrane conductance
Membrane Potentials - drug effects
Molecular and cellular biology
Neurons
Neurons - drug effects
Neurons - physiology
Pipettes
protein kinase
Protein Kinase Inhibitors
Protein Kinases - pharmacology
Protein Kinases - physiology
Retina
Retina - enzymology
Retina - physiology
Roccus chrysops
Second messengers
Vision, photoreception
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Summary:The action of many neuromodulators is mediated by intracellular second messengers such as cyclic AMP. In the retina, exogenously applied dopamine alters the conductance of gap junctions between cultured horizontal cells and this effect is mediated by cyclic AMP. However, it is not known how cyclic AMP modulates horizontal cell gap junction function. Here I report that cyclic AMP works by way of a cyclic AMP-dependent protein kinase. Cyclic AMP-dependent protein kinase injected into coupled horizontal cells from white bass (Roccus chrysops) rapidly and reversibly uncoupled the cells, mimicking the actions of dopamine. The threshold for the effect was between 0.06 and 0.03 μ M. Injection of Walsh inhibitor of protein kinase [Walsh, D. A., Ashby, C. D., Gonzalez, C., Calkins, D., Fischer, E. H. & Krebs, E. G. (1971) J. Biol. Chem. 246, 1977-1985] blocked the effect of dopamine. Thus, the action of dopamine is to raise intracellular levels of cyclic AMP, which then activates a cyclic AMP-dependent protein kinase. Although not tested, it is likely that the cyclic AMP-dependent protein kinase phosphorylates a protein, possibly a gap junction protein, to alter conductance.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.84.20.7319