A series of studies designed to explore the effects of ethanol on neuronal and liposome membrane structure and function are described. Three biochemical-biophysical functions that are associated with brain synaptic membranes are the target of these investigations. The first series of studies will include an examination of ehtanol, other alcohols and local anesthetics on the glutamate receptor-ion channel complex. these involve measurements of ion channel activation in isolated-released synaptic membreanes and in purified glutamate binding protein-reconstituted liposomes. An important component of these studies is the characterization of the effects of membrane lipids on the function of this protein and the changes in lipid-protein interaction produced by ethanol and related agents. A similar approach will be followed with the second and third experimental series which involve and exploration of alcohol effects on the NA+ Ca++ exchange transport and the (Ca++ Mg++)-ATPase of synaptic membranes. Changes in the activity of these two Ca++ buffering systems following modification of membrane lipid organization will be examined in order to evaluate likely targets for the influence of ethanol on these transport carriers. In addition, the molecular motion of the glutamate receptor-like protein and of the (Ca++ Mg++)-ATPase will be measured by electron paramagnetic resonance techniques following reconstitution of these proteins into liposomes. These studies should help us develop an understanding of how the effects of ethanol on protein function are related to changes in the physical state of these proteins within the cell membrane.
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