General anesthetic modulation of neuronal nicotinic acetylcholine receptors

Megumi Yamashita, Takashi Mori, Xilong Zhao, Keiichi Nagata, William Marszalec, Jay Z. Yeh, Toshio Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Inhalational anesthetics are known to modulate various neurotransmitter systems in the brain. Recently, it is becoming abundantly clear that the neuronal nicotinic acetylcholine receptor (nAChR) system is an important target site of anesthetics. However, detailed mechanism of action of anesthetics on the nAChRs remained to be elucidated. We embarked on the patch-clamp analysis of anesthetic interactions with nAChRs at both whole-cell and single-channel levels. Halothane, isoflurane and sevoflurane inhibited the activity of the α4β2 nAChRs in rat cortical neurons in primary culture and in HEK cells expressing the receptors. The inhibition was observed at clinically relevant concentrations of < 1 MAC, and occurred in the resting and activated states of the receptors. The recovery after washing required opening of the channels by ACh. Since nAChRs modulate the activity of various other neurotransmitter systems, anesthetic inhibition of nAChRs is expected to be amplified via a cascade of multisynaptic events in the brain. It is concluded that the nAChRs, especially the α4β2 nAChRs, constitute an important target site of inhalational anesthetics responsible for a variety of behavioral changes associated with general anesthesia.

Original languageEnglish (US)
Pages (from-to)243-246
Number of pages4
JournalInternational Congress Series
Volume1283
DOIs
StatePublished - Nov 2005

Keywords

  • Halothane
  • Inhalational anesthetic
  • Isoflurane
  • Nicotinic acetylcholine receptor
  • Sevoflurane

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'General anesthetic modulation of neuronal nicotinic acetylcholine receptors'. Together they form a unique fingerprint.

Cite this