Alcohol withdrawal upregulates mRNA encoding for Ca(V)2.1-alpha 1 subunit in the rat inferior colliculus

作者：Newton Jamila; Suman Shubhankar; Akinfiresoye Luli R; Datta Kamal; Lovinger David M; N'Gouemo Prosper^*

来源：Alcohol, 2018, 66: 21-26.

DOI：10.1016/j.alcohol.2017.07.007

• Cacna1a
• P/Q-type calcium channel
• Audiogenic seizures

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(V)2.1-alpha 1 (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(V)2.1-alpha 1 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(V)2.1-alpha 1 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(V)2.1-alpha 1 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(V)2.1 channel expression may play a role in AWS pathogenesis.

• 出版日期2018-2