Ethanol acts on KCNK13 potassium channels in the ventral tegmental area to increase firing rate and modulate binge–like drinking

Chang You, Antonia Savarese, Bertha J. Vandegrift, Donghong He, Subhash C. Pandey, Amy Lasek, Mark S. Brodie

Research output: Contribution to journalArticle

Abstract

Alcohol excitation of the ventral tegmental area (VTA) is important in neurobiological processes related to the development of alcoholism. The ionotropic receptors on VTA neurons that mediate ethanol-induced excitation have not been identified. Quinidine blocks ethanol excitation of VTA neurons, and blockade of two-pore potassium channels is among the actions of quinidine. Therefore two-pore potassium channels in the VTA may be potential targets for the action of ethanol. Here, we explored whether ethanol activation of VTA neurons is mediated by the two-pore potassium channel KCNK13. Extracellular recordings of the response of VTA neurons to ethanol were performed in combination with knockdown of Kcnk13 using a short hairpin RNA (shRNA) in C57BL/6 J mice. Real-time PCR and immunohistochemistry were used to examine expression of this channel in the VTA. Finally, the role of KCNK13 in binge-like drinking was examined in the drinking in the dark test after knockdown of the channel. Kcnk13 expression in the VTA was increased by acute ethanol exposure. Ethanol-induced excitation of VTA neurons was selectively reduced by shRNA targeting Kcnk13. Importantly, knockdown of Kcnk13 in the VTA resulted in increased alcohol drinking. These results are consistent with the idea that ethanol stimulates VTA neurons at least in part by inhibiting KCNK13, a specific two-pore potassium channel, and that KCNK13 can control both VTA neuronal activity and binge drinking. KCNK13 is a novel alcohol-sensitive molecular target and may be amenable to the development of pharmacotherapies for alcoholism treatment.

LanguageEnglish (US)
Pages29-36
Number of pages8
JournalNeuropharmacology
Volume144
DOIs
StatePublished - Jan 1 2019

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Binge Drinking
Ventral Tegmental Area
Potassium Channels
Ethanol
Neurons
Quinidine
Small Interfering RNA
Alcoholism
Alcohols
Alcohol Drinking
Action Potentials
Drinking
Real-Time Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Ethanol acts on KCNK13 potassium channels in the ventral tegmental area to increase firing rate and modulate binge–like drinking. / You, Chang; Savarese, Antonia; Vandegrift, Bertha J.; He, Donghong; Pandey, Subhash C.; Lasek, Amy; Brodie, Mark S.

In: Neuropharmacology, Vol. 144, 01.01.2019, p. 29-36.

Research output: Contribution to journalArticle

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