Alcohol withdrawal upregulates mRNA encoding for Ca_V2.1-α1 subunit in the rat inferior colliculus.

We previously reported increased current density through P-type voltage-gated Ca²⁺ channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased P-type channel current is currently unknown. Here, we probe changes in mRNA and protein expression of the pore-forming Ca_V2.1-α1 (P/Q-type) subunits in IC neurons during the course of alcohol withdrawal-induced seizures (AWSs). Rats received three daily doses of ethanol or the vehicle every 8 h for 4 consecutive days. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the Ca_V2.1-α1 subunits were measured. In separate experiments, rats were tested for acoustically evoked seizure susceptibility 3, 24, and 48 h after alcohol withdrawal. AWSs were observed 24 h after withdrawal; no seizures were observed at 3 or 48 h or in the control-treated rats. Compared to control-treated rats, the mRNA levels of the Ca_V2.1-α1 subunit were increased 1.9-fold and 2.1-fold at 3 and 24 h, respectively; change in mRNA expression was nonsignificant at 48 h following alcohol withdrawal. Western blot analyses revealed that protein levels of the Ca_V2.1-α1 subunits were not altered in IC neurons following alcohol withdrawal. We conclude that expression of the Cacna1a mRNA increased before the onset of AWS susceptibility, suggesting that altered Ca_V2.1 channel expression may play a role in AWS pathogenesis.

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