title: Ethanol withdrawal seizure susceptibility is associated with upregulation of L- and P-type Ca2+ channel currents in rat inferior colliculus neurons.
abstract: Calcium currents in the inferior colliculus (IC) are thought to play an important role in ethanol withdrawal hyperexcitability. Here, we report on the modulation of Ca(2+) channel currents in acutely dissociated IC neurons of rats, exhibiting higher incidence of audiogenic seizures when subjected to ethanol withdrawal. Whole cell Ca(2+) channel currents were activated by depolarizing pulses from a holding potential of -90 mV, in 10 mV increments, using barium (Ba(2+)) as the charge carrier. The high threshold voltage-activated (HVA) Ca(2+) channel current density increased significantly in IC neurons following ethanol withdrawal. The gating parameters of HVA Ca(2+) channel currents were only slightly altered, while the fraction of current that did not fully inactivate at positive potentials increased significantly following ethanol withdrawal. Pharmacological dissection of HVA Ca(2+) channel currents suggested that the enhanced current, associated with increased incidence of audiogenic seizures following ethanol withdrawal, was carried by L- and P-type Ca(2+) channels. The upregulation of L- and P-type currents may be responsible for IC neuronal hyperexcitability associated with increased susceptibility to ethanol withdrawal seizures.
authors.affiliation: Department of Pharmacology Georgetown University Medical Center, 3900 Reservoir Rd, NW, Washington, DC 20057, USA.
authors.forename: Prosper
authors.initials: P
authors.lastname: N'Gouemo
authors.forename: Martin
authors.initials: M
authors.lastname: Morad
mesh_terms: D020270:Alcohol Withdrawal Seizures / Q000378:metabolism*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000096:biosynthesis*; D020865:Calcium Channels, P-Type / Q000096:biosynthesis*; D000431:Ethanol / Q000494:pharmacology; D007245:Inferior Colliculi / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; D020865:Calcium Channels, P-Type; D000431:Ethanol