Ethanol withdrawal seizure susceptibility is associated with upregulation of L- and P-type Ca2+ channel currents in rat inferior colliculus neurons.
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.
N'Gouemo
Prosper
P
Department of Pharmacology Georgetown University Medical Center, 3900 Reservoir Rd, NW, Washington, DC 20057, USA.
Morad
Martin
M
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*
D020746:Calcium Channels, L-Type; D020865:Calcium Channels, P-Type; D000431:Ethanol