Altered voltage-gated calcium channels in rat inferior colliculus neurons contribute to alcohol withdrawal 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. (C) 2015 Elsevier B.V. and ECNP All rights reserved.