title: Disrupted thalamic T-type Ca2+ channel expression and function during ethanol exposure and withdrawal.
abstract: Chronic ethanol exposure produces profound disruptions in both brain rhythms and diurnal behaviors. The thalamus has been identified as a neural pacemaker of both normal and abnormal rhythms with low-threshold, transient (T-type) Ca(2+) channels participating in this activity. We therefore examined T-type channel gene expression and physiology in the thalamus of C57Bl/6 mice during a 4-wk schedule of chronic intermittent ethanol exposures in a vapor chamber. We found that chronic ethanol disrupts the normal daily variations of both thalamic T-type channel mRNA levels and alters thalamic T-type channel gating properties. The changes measured in channel expression and function were associated with an increase in low-threshold bursts of action potentials during acute withdrawal periods. Additionally, the observed molecular and physiological alterations in the channel properties in wild-type mice occurred in parallel with a progressive disruption in the normal daily variations in theta (4-9 Hz) power recorded in the cortical electroencephalogram. Theta rhythms remained disrupted during a subsequent week of withdrawal but were restored with the T-type channel blocker ethosuximide. Our results demonstrate that a key ion channel underlying the generation of thalamic rhythms is altered during chronic ethanol exposure and withdrawal and may be a novel target in the management of abnormal network activity due to chronic alcoholism.
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Blvd., Winston Salem, NC 27157, USA. dgodwin@wfubmc.edu
authors.forename: J D
authors.initials: JD
authors.lastname: Graef
authors.forename: T W
authors.initials: TW
authors.lastname: Huitt
authors.forename: B K
authors.initials: BK
authors.lastname: Nordskog
authors.forename: J H
authors.initials: JH
authors.lastname: Hammarback
authors.forename: D W
authors.initials: DW
authors.lastname: Godwin
mesh_terms: D000430:Alcohol Withdrawal Delirium / Q000378:metabolism*; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013788:Thalamus / Q000187:drug effects* / Q000503:physiopathology*
chemical_list: D020747:Calcium Channels, T-Type; D000431:Ethanol