title: Chronic ethanol drinking reduces native T-type calcium current in the thalamus of nonhuman primates.
abstract: BACKGROUND
  Chronic ethanol use is known to disrupt normal sleep rhythms, but the cellular basis for this disruption is unknown. An important contributor to normal sleep patterns is a low-threshold calcium current mediated by T-type calcium channels. The T-type calcium current underlies burst responses in thalamic nuclei that are important to spindle propagation, and we recently observed that this current is sensitive to acute low doses of ethanol.
  
  
  METHODS
  We used a combination of current clamp and voltage clamp recordings in an in vitro brain slice preparation of the dorsal lateral geniculate nucleus (LGN) of macaque monkeys that have chronically self-administered ethanol to determine whether chronic ethanol exposure may affect T-type currents.
  
  
  RESULTS
  Current clamp recordings from the LGN of ethanol naive macaques showed characteristic burst responses. However, recordings from the LGN in macaques that self-administered ethanol revealed a significant attenuation of bursts across a range of voltages (n=5). Voltage clamp recordings from control LGN neurons (n=16) and neurons (n=29) from brain slices from chronically drinking macaques showed no significant differences (P>0.05) in T-type current kinetics or in the membrane resistance of the thalamic cells between the two cohorts. However, mean T-type current amplitude measured in the chronically drinking animals was reduced by 31% (P<0.01).
  
  
  CONCLUSIONS
  We conclude that chronic ethanol self-administration reduces calcium currents in thalamic relay cells without altering underlying current kinetics, which may provide a mechanistic framework for the well-documented disruptions in sleep/wake behavior in subjects with chronic ethanol exposure.
authors.affiliation: Department Anatomical Sciences and Neurobiology, University of Louisville Health Sciences, Louisville, KY 40204, USA.
authors.forename: W Breckinridge
authors.initials: WB
authors.lastname: Carden
authors.forename: Georgia M
authors.initials: GM
authors.lastname: Alexander
authors.forename: David P
authors.initials: DP
authors.lastname: Friedman
authors.forename: James B
authors.initials: JB
authors.lastname: Daunais
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Grant
authors.forename: Jian
authors.initials: J
authors.lastname: Mu
authors.forename: Dwayne W
authors.initials: DW
authors.lastname: Godwin
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000503:physiopathology; D000437:Alcoholism / Q000150:complications*; D000818:Animals; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012893:Sleep Wake Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D013788:Thalamus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D020747:Calcium Channels, T-Type; D002492:Central Nervous System Depressants; D000431:Ethanol