Premium
BK Channel β 1 Subunit Contributes to Behavioral Adaptations Elicited by Chronic Intermittent Ethanol Exposure
Author(s) -
Kreifeldt Max,
CatesGatto Chelsea,
Roberts Amanda J.,
Contet Candice
Publication year - 2015
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12911
Subject(s) - protein subunit , ethanol , bk channel , neuroscience , psychology , chemistry , biochemistry , membrane potential , gene
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 β 1 and β 4 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 β 1 and β 4 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 β 1 or β 4 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 β 1 deletion reduced chronic tolerance to sedation and abolished chronic tolerance to hypothermia, while BK β 4 deletion did not affect these adaptations to chronic EtOH exposure. Finally, the absence of BK β 1 accelerated the appearance, while the absence of BK β 4 delayed the resolution, of the hyperexcitable state associated with EtOH withdrawal. Conclusions Altogether, the present findings reveal the critical role of BK β 1 in behavioral adaptations to prolonged, repeated EtOH intoxication.