Altered voltage-gated calcium channels in rat inferior colliculus neurons contribute to alcohol withdrawal seizures

作者：N' Gouemo Prosper

来源：European Neuropsychopharmacology, 2015, 25(8): 1342-1352.

DOI：10.1016/j.euroneuro.2015.04.008

• omega-Agatoxin TK
• Nifedipine
• Nimodipine
• Calcium channels
• Current density
• Generalized tonicclonic seizures

We have previously reported that enhanced susceptibility to alcohol withdrawal seizures (AWS) parallels the enhancement of the current density of high-threshold voltage-gated Ca2+ (Ca-V) channels in rat inferior colliculus (IC) neurons. However, whether this increased current density is a cause or consequence of AWS is unclear. Here, I report changes in the current density of Ca-V channels in IC neurons during the course of alcohol withdrawal and the potential anticonvulsant effect of intra-IC infusions of L- and P-type Ca-V channel antagonists. Whole-cell currents were activated by depolarizing pulses using barium as the charge carrier. Currents and seizure susceptibility were evaluated in control animals 3 h after alcohol intoxication, as well as 3 h (before AWS), 24 h (when AWS susceptibility is maximal), and 48 h (when AWS susceptibility is no longer present) after alcohol withdrawal. Nifedipine, nimodipine (L-type antagonists) or omega-agatoxin TK (P-type antagonist) were infused intra-IC to probe the role of Ca-V channels in the pathogenesis of AWS. Ca-V current density and conductance in IC neurons were significantly increased 3 and 24 h after alcohol withdrawal compared with the control group or the group tested 3 h following ethanol intoxication. Blockade of L-type Ca-V channels within the IC completely suppressed AWS, and inhibition of P-type channels reduced AWS severity. These findings suggest that the enhancement of Ca-V currents in IC neurons occurs prior to AWS onset and that alterations in L- and P-type Ca-V channels in these neurons may underlie the pathogenesis of AWS.

• 出版日期2015-8