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

Alejandro Dopico, Anna Bukiya, Jill C. Bettinger

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Title of host publicationHandbook of Experimental Pharmacology
PublisherSpringer New York LLC
Pages281-309
Number of pages29
DOIs
StatePublished - Jan 1 2018

Publication series

NameHandbook of Experimental Pharmacology
Volume248
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Fingerprint

Potassium Channels
Neurons
Ethanol
Genes
Alcohols
Electric potential
Invertebrates
Physiology
Voltage-Gated Potassium Channels
Neurobiology
Ion Channels
Accessories
Vertebrates
Rodentia
Extrapolation
Proteins
Calcium
Blood
Modulation
Networks (circuits)

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Dopico, A., Bukiya, A., & Bettinger, J. C. (2018). Voltage-Sensitive Potassium Channels of the BK Type and Their Coding Genes Are Alcohol Targets in Neurons. In Handbook of Experimental Pharmacology (pp. 281-309). (Handbook of Experimental Pharmacology; Vol. 248). Springer New York LLC. https://doi.org/10.1007/164_2017_78

Voltage-Sensitive Potassium Channels of the BK Type and Their Coding Genes Are Alcohol Targets in Neurons. / Dopico, Alejandro; Bukiya, Anna; Bettinger, Jill C.

Handbook of Experimental Pharmacology. Springer New York LLC, 2018. p. 281-309 (Handbook of Experimental Pharmacology; Vol. 248).

Research output: Chapter in Book/Report/Conference proceedingChapter

Dopico, A, Bukiya, A & Bettinger, JC 2018, Voltage-Sensitive Potassium Channels of the BK Type and Their Coding Genes Are Alcohol Targets in Neurons. in Handbook of Experimental Pharmacology. Handbook of Experimental Pharmacology, vol. 248, Springer New York LLC, pp. 281-309. https://doi.org/10.1007/164_2017_78
Dopico A, Bukiya A, Bettinger JC. Voltage-Sensitive Potassium Channels of the BK Type and Their Coding Genes Are Alcohol Targets in Neurons. In Handbook of Experimental Pharmacology. Springer New York LLC. 2018. p. 281-309. (Handbook of Experimental Pharmacology). https://doi.org/10.1007/164_2017_78
Dopico, Alejandro ; Bukiya, Anna ; Bettinger, Jill C. / Voltage-Sensitive Potassium Channels of the BK Type and Their Coding Genes Are Alcohol Targets in Neurons. Handbook of Experimental Pharmacology. Springer New York LLC, 2018. pp. 281-309 (Handbook of Experimental Pharmacology).
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