Single-channel analyses of ethanol modulation of neuronal nicotinic acetylcholine receptors

Yi Zuo, Keiichi Nagata, Jay Z. Yeh, Toshio Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: We have previously reported that ethanol potentiates the acetylcholine-induced currents of the α4β2 neuronal nicotinic acetylcholine receptors in rat cortical neurons and of those that are stably expressed in human embryonic kidney cells. The potentiation of the maximal currents evoked by high concentrations of acetylcholine suggests that ethanol affects the channel gating. Methods: We performed single-channel patch-clamp experiments to elucidate the detailed mechanism of ethanol modulation of the α4β2 receptor that is stably expressed in human embryonic kidney cells. Results: At least two conductance states, 40.5 pS and 21.9 pS, were activated by acetylcholine. Acetylcholine at 30 nM predominantly induced the high conductance state currents (85% of total). Ethanol did not affect the single-channel conductance but selectively modulated the high-conductance state currents. The high-conductance state currents exhibited two open time constants. Both time constants were increased by 100 mM ethanol, from 1.9 msec to 2.8 msec and from 9.0 msec to 15.5 msec, respectively. Ethanol also prolonged the burst duration and the open time within burst and increased the probability of channel opening. Conclusions: These changes in single-channel parameters indicate that ethanol stabilizes the α4β2 receptor-channel in the opening state, explaining how the maximum acetylcholine-induced whole-cell currents are further potentiated by ethanol.

Original languageEnglish (US)
Pages (from-to)688-696
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume28
Issue number5
DOIs
StatePublished - May 2004

Keywords

  • Acetylcholine Receptor
  • Alcohol
  • Ethanol
  • Single Channel
  • α4β2 Receptor

ASJC Scopus subject areas

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

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