Alcohol modulation of neuronal nicotinic acetylcholine receptors is α subunit dependent

Yi Zuo, Alexander Kuryatov, Jon M. Lindstrom, Jay Z. Yeh, Toshio Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background: We have previously shown that n-alcohols exert a dual action on the α4β2-type neuronal nicotinic acetylcholine (ACh) receptors (AChRs), with shorter-chain alcohols potentiating and longerchain alcohols inhibiting ACh-induced currents. Ethanol potentiates the current in α4β2 receptors, yet it has little or no effect on the α3β2 receptors. Because the α4 AChRs are present predominantly in the brain, whereas the α3 AChRs are present predominantly in the peripheral ganglia, the differential action of ethanol on the α4β2 and α3β2 AChRs may contribute to its differential effects on the brain and the peripheral nervous system. The purpose of this study was to characterize the actions of alcohols on an α3-containing nicotinic receptor and to further understand the mechanism underlying the differential action of ethanol on the two receptor subtypes. Methods: ACh-induced currents were recorded from human α3β2 AChRs recombinantly expressed in human embryonic kidney tsA201 cells by using the whole-cell patch clamp technique. Results: The ACh-induced currents in the α3β2 receptors were potentiated by methanol and inhibited by longer-chain alcohols. The transition point from potentiation to inhibition and the cutoff point were both shifted to shorter alcohols in the α3β2 AChR compared with the α4β2 AChR. This explains why ethanol, which was at the transition point, has little or no effect on the α3β2 AChR. Conclusions: The α3β2 AChRs are insensitive to ethanol because ethanol is at the transition point from potentiation to inhibition among n-alcohols with different carbon-chain lengths. The differential action on the α4β2 and α3β2 AChRs may explain the differential action of ethanol on the central nervous system.

Original languageEnglish (US)
Pages (from-to)779-784
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume26
Issue number6
DOIs
StatePublished - 2002

Keywords

  • Alcohol
  • Ethanol
  • HEK Cells
  • αβ Neuronal Nicotinic ACh Receptor
  • αβ Neuronal Nicotinic ACh Receptor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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