Single Channel Characterization of Ethanol Action on the Glycine Receptor

University Of Texas At Austin, Austin TX

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Abstract

DESCRIPTION (provided by applicant): Understanding the mechanisms and targets of ethanol's actions throughout the brain and central nervous system is a critical piece in the quest to understand the complex pharmacology of ethanol. Among ethanol's diverse targets is the glycine receptor (GlyR);an inhibitory, ligand gated ion channel that is found heavily expressed throughout the brain stem and spinal cord in addition to higher brain regions, including those involved in addiction. Despite numerous studies examining the effects of ethanol on the glycine receptor, very little has been done to characterize its actions on the molecular level. We propose to use patch clamp electrophysiology to investigate the effects of ethanol on the single channel properties of the wild-type GlyR and use targeted mutations to further understand the mechanisms of ethanol enhancement of GlyR function. The long-range goal is to provide a molecular framework for understanding ethanol's actions on the GlyR population within the central nervous system and how ethanol's modulation of the GlyR contributes to its in vivo effects. This proposed research provides a definitive step towards attaining this understanding with the objective of demonstrating specifically how ethanol enhances GlyR function at the single channel level. In order to develop appropriate and effective treatments of alcoholism it is necessary to understand how ethanol exerts its effects throughout the body. This research could not only lead to better treatments for alcoholism, but will enhance our understanding of alcohol's actions throughout the central nervous system.