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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.