Effect of chronic ethanol exposure on the electric membrane properties of DRG neurons in cell culture

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Abstract
Neural cell cultures of adult mouse dorsal root ganglia were utilized to investigate the effects of chronic ethanol exposure on neuronal electric membrane properties (EMP). After 12 days of exposure to various ethanol concentrations, the EMP of the neurons were determined in ethanol-free medium. Significant changes in a number of EMP were observed. Of particular physiological significance were decreased specific membrane resistance, increased specific membrane capacitance, relatively little change in membrane time constant, and increased electrical excitability. Various features of the action potential were also affected, e.g., reduced overshoot, afterhyperpolarization, and rate of rise. In preliminary experiments, EMP were determined at varying periods after the cultures had been withdrawn from ethanol medium and maintained in ethanol-free medium. These results indicated that the altered EMP persisted as long as one (Cm) to two (Rm) weeks after ethanol withdrawal. A possible mechanism for these ethanol-induced changes in EMP was suggested, utilizing the membrane expansion theory of anesthesia. Because of few previous reports demonstrating significant electrophysiological effects of ethanol at pharmacological concentrations, the neural cell culture system provides a useful new experimental model for studying the action of chronic ethanol exposure on neuronal EMP and the physical basis of the tolerance and withdrawal phenomena found in alcoholism and addiction in general. After being maintained for 12 days in culture media containing various concentrations of ethanol, non-neuronal cell survival was observed to have decreased in an approximately linear manner with increasing ethanol levels. By contrast, neuron survival was not affected until ethanol concentrations greater than 0.34 g % were used. This decreased cell survival due to chronic exposure to physiological levels of ethanol has not been reported previously. Neural cell cultures may therefore be useful for investigating the cellular pathology of chronic alcoholism and fetal alcohol syndrome.