Isoflurane modulation of neuronal nicotinic acetylcholine receptors expressed in human embryonic kidney cells

Megumi Yamashita, Takashi Mori, Keiichi Nagata, Jay Z. Yeh, Toshio Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Background: It is well established that neuronal nicotinic acetylcholine receptors (nAChRs) are sensitive to inhalational anesthetics. The authors previously reported that halothane potently blocked α4β2-type nAChRs of rat cortical neurons. However, the effect of isoflurane, which is widely used clinically, on nAChRs largely remains to be seen. The authors studied the effects of isoflurane as compared with sevoflurane and halothane on the human α4β2 nAChRs expressed in human embryonic kidney cells. Methods: The whole-cell and single-channel patch clamp techniques were used to record currents induced by acetylcholine. Results: Isoflurane, sevoflurane, and halothane suppressed the acetylcholine-induced currents in a concentration-dependent manner with 50% inhibitory concentrations of 67.1, 183.3, and 39.8 μM, respectively, which correspond to 0.5 minimum alveolar concentration or less. When anesthetics were coapplied with acetylcholine, isoflurane and sevoflurane decreased the apparent affinity of receptor for acetylcholine, but halothane, in addition, decreased the maximum acetylcholine current. When isoflurane was preapplied and coapplied, its inhibitory action was independent of acetylcholine concentration. Isoflurane blocked the nAChR in both resting and activated states. Single-channel analyses revealed that isoflurane at 84 μM decreased the mean open time and burst duration without inducing "flickering" during channel openings. Isoflurane increased the mean closed time. As a result, the open probability of single channels was greatly reduced by isoflurane. Conclusions: Isoflurane, sevoflurane, and halothane potently blocked the α4β2 nAChR. Isoflurane suppression of whole-cell acetylcholine currents was a result of decreases in the open time, burst duration, and open probability and an increase in the closed time of single channels. The high sensitivity of neuronal nAChRs to inhalational anesthetics is expected to play an important role in several stages of anesthesia.

Original languageEnglish (US)
Pages (from-to)76-84
Number of pages9
JournalAnesthesiology
Volume102
Issue number1
DOIs
StatePublished - Jan 2005

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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