Increase in expression of alpha1 and alpha2/delta1 subunits of L-type high voltage-gated calcium channels after sustained ethanol exposure in cerebral cortical neurons

J Pharmacol Sci. 2006 Oct;102(2):221-30. doi: 10.1254/jphs.fp0060781. Epub 2006 Oct 7.

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 alpha1C, alpha1D, and alpha2/delta1 subunits with decreased beta4 subunit expression and no changes in expressions of alpha1A, alpha1B, alpha1F, and alpha2 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 alpha1C, alpha1D, and alpha2/delta1 subunits, and produces no alterations in P/Q- and N-type HVCC functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism / metabolism*
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type / metabolism*
  • Calcium Channels, N-Type
  • Calcium Channels, P-Type / metabolism*
  • Calcium Channels, Q-Type / metabolism*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Dose-Response Relationship, Drug
  • Ethanol / toxicity*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neurons / drug effects*
  • Neurons / metabolism
  • Time Factors

Substances

  • CACNA2D1 protein, mouse
  • Cacna1d protein, mouse
  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • Calcium Channels, P-Type
  • Calcium Channels, Q-Type
  • voltage-dependent calcium channel (P-Q type)
  • Ethanol
  • Calcium