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Abstract. Previous reports revealed up-regulation of L-type high voltage-gated calcium channels (HVCCs) in mouse brains with ethanol physical dependence. We investigated mechanisms of enhancement of L-type HVCC function using mouse cerebrocortical neurons exposed to 50 mM ethanol for 3 days and the brains of mouse physically dependent on ethanol. Ethanol facilitated 30 mM KCl-stimulated 45 Ca 2+ influx in dose-and duration-dependent manners, which was abolished by nifedipine, an inhibitor specific to L-type HVCCs, but not by inhibitors for other types of HVCCs. Increase in [3 H]PN200-110 binding to the particulate fractions from the ethanol-treated neurons was due to increased B max value with no changes in K d value. Western blot analysis showed the increased expression of α1C, α1D, and α2/ δ1 subunits with decreased β4 subunit expression and no changes in expressions of α1A, α1B, α1F, and α2 subunits. A similar pattern of the changes in the expression of these subunits of L-type HVCCs were observed in the cerebral cortex from mouse with ethanol physical dependence. These results indicate that sustained ethanol exposure to the neurons induces up-regulation of L-type HVCCs, which is due to increased expressions of α1C, α1D, and α2 / δ1 subunits, and produces no alterations in P / Q-and N-type HVCC functions.

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