The overall goal of this project is to determine the extent to which membrane-dependent activities of neuronal cells are altered by changes in membrane lipid composition. Changes in membrane lipid composition will be induced by physiologically-relevant manipulation of there availability of membrane precursors in the culture medium of clonal neuroal cells. Initial experiments have demonstrated that changes in the availability of unsaturated fatty acids causes changes in depolarization-dependent exocytosis, action potential generation and receptor binding characteristics.
The specific aims of the project will be: 1. continue characterizing these changes to uncover mechanistic explanations for them, 2. examine the effects of alterations in phospholipid composition on several other membrane-dependent functions, including transport systems for norepinephrine, choline and glucose, 3. alter the cellular membrane content of cholesterol and various phospholipid classes, 4. study the effects of these other lipid modifications on the exocytosis and transport phenomena in the cells, 5. extend these studies to non-tumor cells, namely isolated adrenal chromaffin cells in culture. These studies will require integration of techniques and principles of biochemistry, pharmacology and cell biology. Completion of this work will provide new insights into membrane composition/function relationships in general. Most specifically, they should provide a strong framework from which to determine if membrane lipid changes of the type inducible by dietary lipid changes should be considered as potential modifiers of fundamental cellular activities.
| Love, J A; Saum, W R; McGee Jr, R (1985) The effects of exposure to exogenous fatty acids and membrane fatty acid modification on the electrical properties of NG108-15 cells. Cell Mol Neurobiol 5:333-52 |
