Voltage-Sensitive Potassium Channels of the BK Type and Their Coding Genes Are Alcohol Targets in Neurons

  • Alex M. DopicoEmail author
  • Anna N. Bukiya
  • Jill C. Bettinger
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 248)


Among all members of the voltage-gated, TM6 ion channel superfamily, the proteins that constitute calcium- and voltage-gated potassium channels of large conductance (BK) and their coding genes are unique for their involvement in ethanol-induced disruption of normal physiology and behavior. Moreover, in vitro studies document that BK activity is modified by ethanol with an EC50~23 mM, which is near blood alcohol levels considered legal intoxication in most states of the USA (0.08 g/dL = 17.4 mM). Following a succinct introduction to our current understanding of BK structure and function in central neurons, with a focus on neural circuits that contribute to the neurobiology of alcohol use disorders (AUD), we review the modifications in organ physiology by alcohol exposure via BK and the different molecular elements that determine the ethanol response of BK in alcohol-naïve systems, including the role of an ethanol-recognizing site in the BK-forming slo1 protein, modulation of accessory BK subunits, and their coding genes. The participation of these and additional elements in determining the response of a system or an organism to protracted ethanol exposure is consequently analyzed, with insights obtained from invertebrate and vertebrate models. Particular emphasis is put on the role of BK and coding genes in different forms of tolerance to alcohol exposure. We finally discuss genetic results on BK obtained in invertebrate organisms and rodents in light of possible extrapolation to human AUD.


Alcohol KCNMB genes MaxiK channel Neuron Slo1 and orthologs 





Acute functional tolerance




2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid


Action potential


Alcohol use disorders


Voltage- and calcium-gated potassium channel of large conductance


Voltage-gated calcium channel


Chronic intermittent ethanol


Cerebellar Purkinje cell


Cytosolic tail domain






Ligand concentration at which 50% of the ligand’s maximal effect is reached


Fast afterhyperpolarization


4-Aminobutanoic acid




Handling-induced convulsions


Macroscopic current








Voltage-gated potassium channel


Loss of righting reflex


Medium spiny neuron




Pore-gate domain


Protein kinase A


Open probability




Regulatory of conductance for potassium


Suprachiasmatic neurons


Substantia nigra




Voltage-sensor domain


Ventro-tegmental area



This work was supported by the National Institute of Alcohol Abuse and Alcoholism through grants R37-AA11560 (AD), R01 AA-023764 (AB), and R01 AA-024482 (JB).


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© Springer International Publishing AG 2017

Authors and Affiliations

  • Alex M. Dopico
    • 1
    Email author
  • Anna N. Bukiya
    • 1
  • Jill C. Bettinger
    • 2
  1. 1.Department of PharmacologyCollege of Medicine, The University of Tennessee Health Science CenterMemphisUSA
  2. 2.Department of Pharmacology and ToxicologyVirginia Commonwealth UniversityRichmondUSA

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