title: BK Channel β1 Subunit Contributes to Behavioral Adaptations Elicited by Chronic Intermittent Ethanol Exposure.
abstract: BACKGROUND
  Large conductance, calcium- and voltage-activated potassium (BK) channels regulate neuronal excitability and neurotransmission. They can be directly activated by ethanol (EtOH) and they may be implicated in EtOH dependence. In this study, we sought to determine the influence of the auxiliary β1 and β4 subunits on EtOH metabolism, acute sensitivity to EtOH intoxication, acute functional tolerance, chronic tolerance, and handling-induced convulsions during withdrawal.
  
  
  METHODS
  Motor coordination, righting reflex, and body temperature were evaluated in BK β1 and β4 knockout, heterozygous, and wild-type mice following acute EtOH administration. Chronic tolerance and physical dependence were induced by chronic intermittent inhalation of EtOH vapor.
  
  
  RESULTS
  Constitutive deficiency in BK β1 or β4 subunits did not alter the clearance rate of EtOH, acute sensitivity to EtOH-induced ataxia, sedation, and hypothermia, nor acute functional tolerance to ataxia. BK β1 deletion reduced chronic tolerance to sedation and abolished chronic tolerance to hypothermia, while BK β4 deletion did not affect these adaptations to chronic EtOH exposure. Finally, the absence of BK β1 accelerated the appearance, while the absence of BK β4 delayed the resolution, of the hyperexcitable state associated with EtOH withdrawal.
  
  
  CONCLUSIONS
  Altogether, the present findings reveal the critical role of BK β1 in behavioral adaptations to prolonged, repeated EtOH intoxication.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California.
authors.forename: Max
authors.initials: M
authors.lastname: Kreifeldt
authors.affiliation: Molecular and Cellular Neuroscience Department, The Scripps Research Institute, La Jolla, California.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Cates-Gatto
authors.affiliation: Molecular and Cellular Neuroscience Department, The Scripps Research Institute, La Jolla, California.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Roberts
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California.
authors.forename: Candice
authors.initials: C
authors.lastname: Contet
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D006993:Hypnotics and Sedatives / Q000633:toxicity*; D007035:Hypothermia / Q000139:chemically induced*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits / Q000502:physiology*
chemical_list: D006993:Hypnotics and Sedatives; D051036:Large-Conductance Calcium-Activated Potassium Channels; D021122:Protein Subunits; D000431:Ethanol
keywords: Alcohol; Dependence; Intoxication; Knockout Mice; Vapor Chambers