Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter found throughout mammalian central nervous system. Activation of a class of postsynaptic receptors (GABAA receptors) by GABA leads to a fast and transient increase in chloride (Cl-) current that results in membrane hyperpolarization or depolarization. This membrane response is an effective mechanism to reduce postsynaptic membrane excitability as action potential firing is inhibited. The increase on Cl- conductance associated to the activation of GABA-A receptors is subject to modulation by barbiturates and benzodiazepines which can increase the Cl- conductance by acting at distinct but interacting sites on the GABA receptor- Cl- ion channel complex. Biochemical and behavioral studies have suggested that pharmacologically relevant concentrations of ethanol can potentiate the function of the GABA receptor- Cl- ion channel complex in the brain. Electrophysiological experiments at the neuronal level have found that ethanol may enhance, depress or have no effect on GABA-mediated responses suggesting cellular diversity or the existence of a complex interaction between ethanol and GABA receptors. In spite of the attempts to gain insights on this action of ethanol no information is presently available on the site of action of ethanol (glial or neuronal receptors), or on the mechanism by which ethanol may interact with the GABA-A receptor at the cellular level. The primary objective of this project is the characterization of the actions of ethanol on the GABA-activated Cl- current in mammalian hippocampal, cortical and spinal cord neurons using the patch-clamp technique. In addition, the influence of various modulators on the function of GABA-A receptors will also be investigated. Such information may be important in understanding the cellular basis for ethanol intoxication and its interaction at the cellular level with benzodiazepine and barbiturates.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Biochemistry, Physiology and Medicine Subcommittee (ALCB)
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Catholic University of Valparaiso
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