Elevation of Basal Protein Kinase C Activity Increases Ethanol Sensitivity of GABAA Receptors in Rat Hippocampal CA1 Pyramidal Neurons

: The ability of ethanol to enhance GABAA receptor function remains controversial; conflicting observations have been made even in the same brain region, and when using apparently similar methodologies. In this study we characterized a single protocol variable, the initial incubation temperature of...

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Bibliographic Details
Published in:Journal of neurochemistry 1997-05, Vol.68 (5), p.1949-1959
Main Authors: Weiner, J. L., Valenzuela, C. F., Watson, P. L., Frazier, C. J., Dunwiddie, T. V.
Format: Article
Language:eng ; jpn
Subjects:
Biological and medical sciences
Ethanol
GABAA receptor
Hippocampus
Inhibitory postsynaptic current
Medical sciences
Protein kinase C
Tobacco, tobacco smoking
Toxicology
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Summary:: The ability of ethanol to enhance GABAA receptor function remains controversial; conflicting observations have been made even in the same brain region, and when using apparently similar methodologies. In this study we characterized a single protocol variable, the initial incubation temperature of brain slices, that had dramatic effects on the ethanol sensitivity of GABAA inhibitory postsynaptic currents (IPSCs) recorded from rat hippocampal CA1 pyramidal neurons. Incubation of hippocampal slices at relatively low temperatures (11–15°C) immediately after slice preparation significantly affected a number of physiological and biochemical parameters. Such slices showed a decrease in extracellular inhibitory postsynaptic potential amplitude, a significant increase in the ethanol sensitivity of GABAA IPSCs in CA1 pyramidal neurons, no change in pentobarbital or flunitrazepam potentiation of IPSCs, and an increase in basal protein kinase C (PKC) activity relative to slices incubated at 31–33°C. In addition, the increase in ethanol sensitivity of GABAA IPSCs was blocked by chelerythrine, a selective inhibitor of PKC. These results suggest that differences in hippocampal slice incubation protocols may have contributed to the disparate results of previous investigations of ethanol modulation of GABAA receptor‐mediated synaptic transmission in the rat hippocampus. In addition, these findings provide further evidence that PKC activity positively modulates the interaction between ethanol and GABAA receptors in the mammalian brain.
ISSN:0022-3042
1471-4159
DOI:10.1046/j.1471-4159.1997.68051949.x