Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of Ca(V)1.3 Channels in the Rat Inferior Colliculus

BACKGROUND: We previously reported increased current density through L-type voltage-gated Ca(2+) (Ca(V)1) channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased Ca(V)1 current is currently unknown. METHODS: Rats received three daily doses of ethanol every 8 hours for 4 consecutive days; control rats received vehicle. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the Ca(V)1.3 and Ca(V)1.2 α1 subunits were measured. In separate experiments, rats were tested for their susceptibility to alcohol withdrawal–induced seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal. RESULTS: In the alcohol-treated group, AWS were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours. No seizures were observed at any time in the control-treated rats. Compared to control-treated rats, the mRNA level of the Ca(V)1.3 α1 subunit was increased 1.4-fold, 1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast, the mRNA level of the Ca(V)1.2 α1 subunit increased 1.5-fold and 1.4-fold at 24 and 48 hours, respectively. At 24 hours, Western blot analyses revealed that the levels of the Ca(V)1.3 and Ca(V)1.2 α1 subunits increased by 52% and 32%, respectively, 24 hours after alcohol withdrawal. In contrast, the Ca(V)1.2 and Ca(V)1.3 α1 subunits were not altered at either 3 or 48 hours during alcohol withdrawal. CONCLUSIONS: Expression of the Ca(V)1.3 α1 subunit increased in parallel with AWS development, suggesting that altered L-type Ca(V)1.3 channel expression is an important feature of AWS pathogenesis.