title: Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus.
abstract: BACKGROUND
  We previously reported increased current density through L-type voltage-gated Ca(2+) (CaV1) channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased CaV1 current is currently unknown.
  
  
  METHODS
  Rats received three daily doses of ethanol every 8 hours for 4 consecutive days; control rats received vehicle. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV1.3 and CaV1.2 α1 subunits were measured. In separate experiments, rats were tested for their susceptibility to alcohol withdrawal-induced seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal.
  
  
  RESULTS
  In the alcohol-treated group, AWS were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours. No seizures were observed at any time in the control-treated rats. Compared to control-treated rats, the mRNA level of the CaV1.3 α1 subunit was increased 1.4-fold, 1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast, the mRNA level of the CaV1.2 α1 subunit increased 1.5-fold and 1.4-fold at 24 and 48 hours, respectively. At 24 hours, Western blot analyses revealed that the levels of the CaV1.3 and CaV1.2 α1 subunits increased by 52% and 32%, respectively, 24 hours after alcohol withdrawal. In contrast, the CaV1.2 and CaV1.3 α1 subunits were not altered at either 3 or 48 hours during alcohol withdrawal.
  
  
  CONCLUSIONS
  Expression of the CaV1.3 α1 subunit increased in parallel with AWS development, suggesting that altered L-type CaV1.3 channel expression is an important feature of AWS pathogenesis.
authors.affiliation: Georgetown University Medical Center, Department of Pediatrics, Washington DC (Drs N'Gouemo and Akinfiesoye); Howard University College of Medicine, Department of Physiology & Biophysics, Washington DC (Dr Allard); Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (Dr Lovinger). pn@georgetown.edu.
authors.forename: Prosper
authors.initials: P
authors.lastname: N'Gouemo
authors.affiliation: Georgetown University Medical Center, Department of Pediatrics, Washington DC (Drs N'Gouemo and Akinfiesoye); Howard University College of Medicine, Department of Physiology & Biophysics, Washington DC (Dr Allard); Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (Dr Lovinger).
authors.forename: Luli R
authors.initials: LR
authors.lastname: Akinfiresoye
authors.affiliation: Georgetown University Medical Center, Department of Pediatrics, Washington DC (Drs N'Gouemo and Akinfiesoye); Howard University College of Medicine, Department of Physiology & Biophysics, Washington DC (Dr Allard); Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (Dr Lovinger).
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Allard
authors.affiliation: Georgetown University Medical Center, Department of Pediatrics, Washington DC (Drs N'Gouemo and Akinfiesoye); Howard University College of Medicine, Department of Physiology & Biophysics, Washington DC (Dr Allard); Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (Dr Lovinger).
authors.forename: David M
authors.initials: DM
authors.lastname: Lovinger
mesh_terms: D020270:Alcohol Withdrawal Seizures / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000145:classification / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000633:toxicity; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D007245:Inferior Colliculi / Q000166:cytology* / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C504728:Cacna1c protein, rat; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002492:Central Nervous System Depressants; D012333:RNA, Messenger; C093712:Cacna1d protein, rat; D000431:Ethanol
keywords: Cacna1c mRNA; Cacna1d mRNA; Cav1.2 α1 subunit; Cav1.3 α1 subunit; alcohol withdrawal seizures