Isoflurane and sevoflurane interact with the nicotinic acetylcholine receptor channels in micromolar concentrations

Michaela Scheller, Johannes Bufler, Hajo Schneck, Eberhard Kochs, Christian Franke

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Background: This study was performed to elucidate and compare the effects of sevoflurane and of isoflurane on the nicotinic acetylcholine receptor of mouse myotubes. The experiments were done with special reference to anesthetic concentrations considerably less than those used for clinical anesthesia. Methods: The patch-clamp technique was used to record acetylcholine-activated currents from the embryonic type of the nicotinic acetylcholine receptor in the outside-out mode. A piezo-driven liquid filament switch was used for the ultrafast application of acetylcholiue alone or in combination with isoflurane or sevoflurane. In addition, the patches were preexposed to either anesthetic, preceding the activation with acetylcholine. Results: The current elicited by acetylcholine was reduced reversibly and in a concentration-dependent manner by both anesthetics, which were equally effective. Preexposure of the patches to isoflurane or sevoflurane showed an additional inhibition that was present at micromolar concentrations. The time courses of current decay could be fitted by single exponentials for isoflurane. At higher concentrations of sevoflurane, the current decay became biexponential. In contrast to isoflurane, sevoflurane increased the time constants of desensitization when applied in low concentrations. Conclusions: At the nicotinic acetylcholine receptor, isoflurane and sevoflurane act primarily through the same mechanisms: Both affect the open and the closed state of the channels in concentrations equal to and less than those encountered clinically. The kinetics of desensitization, however, are altered in a different manner. Thus there may be several different sites of interaction.

Original languageEnglish
Pages (from-to)118-127
Number of pages10
JournalAnesthesiology
Volume86
Issue number1
DOIs
StatePublished - 1997

Keywords

  • Anesthesia: mechanism
  • Anesthetics: isoflurane; sevoflurane
  • Equipment: fast application system; patch clamp
  • Receptors: nicotinic acetylcholine

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