Octanol modulation of neuronal nicotinic acetylcholine receptor single channels

Yi Zuo, Jay Z. Yeh, Toshio Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: We have previously shown that alcohols exert a dual action on neuronal nicotinic acetylcholine receptors (AChRs), with short-chain alcohols potentiating and long-chain alcohols inhibiting acetylcholine (ACh)-induced whole-cell currents. At the single-channel level, ethanol increased the channel open probability and prolonged the channel open time and burst duration. In this study, we examined the detailed mechanism of the inhibitory action of the long-chain alcohol n-octanol on the neuronal nicotinic AChR. Methods: Single-channel currents induced by application of 30 nM ACh were recorded with the patch-clamp technique from human embryonic kidney cells stably expressing the human α4β2 AChR. Results: Several single-channel parameters were markedly changed by octanol. At least two conductance-state currents were induced by low concentrations of ACh, and octanol increased the proportion of the low-conductance-state current relative to the high-conductance-state current without changing the current amplitude. Major analyses of temporal properties of single-channel currents were performed on the high-conductance-state currents. Octanol decreased the burst duration and duration of openings within burst and prolonged the mean closed time. All of these changes contributed to the decrease in the open probability in a concentration-dependent manner. Conclusions: Several aspects of octanol action on neuronal AChRs at the single-channel level are compatible with an atypical open channel block model reported with muscle nicotinic AChRs. The potentiating action of short-chain alcohols and the inhibitory action of long-chain alcohols on the neuronal nicotinic AChR are mediated through different mechanisms.

Original languageEnglish (US)
Pages (from-to)1648-1656
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume28
Issue number11
DOIs
StatePublished - Nov 2004

Keywords

  • Acetylcholine Receptor
  • Alcohol
  • Octanol
  • Single Channel

ASJC Scopus subject areas

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

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