This research is intended to provide information on changes that occur in plasma membranes of mammalian cells during and after exposure of such cells to elevated temperatures. The hypothesis to be tested is that these changes are, at least in part, responsible for cell death at hyperthermic temperature and, perhaps also, for the induction of thermotolerance. To this end, four sets of experiments are performed: 1) The cytotoxic action of detergents and phospholipid analogs is tested at elevated temperatures. These compounds have a wide range of lipophilicities and critical micelle concentrations. 2) The cytotoxic action of stearic acid doxyl probes is used to test for transmembrane locations of heat-sensitive sites. 3) The response of ion channels to electrical stimulation is examined at hyperthermic temperatures. These experiments involve both ion-specific and nonspecific electrodes. Operation of the individual ion channels is characterized as a function of temperature. 4) Epithelial cells are used to identify the role that cell-to-cell contact (as distinct from cell density) plays in modifying response of cells to heat. Overall, these sets of experiments are intended to locate heat sensitive sites within the plasma membrane, identify specific proteins there that are affected by heat, and test how functional membrane modifications affect heat response.
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