Comparative presynaptic effects of the volatile anesthetics sevoflurane and isoflurane at the mouse neuromuscular junction

Muscle Nerve. 2015 Nov;52(5):876-84. doi: 10.1002/mus.24589. Epub 2015 Aug 13.

Abstract

Introduction: Sevoflurane and isoflurane are anesthetics that cause muscle relaxation and potentiate the effects of neuromuscular blocking agents. Their presynaptic mechanisms of action are not understood completely, especially at the motor nerve terminal.

Methods: We compared the presynaptic effects of these anesthetics on the exocytosis of synaptic vesicles labeled with the dye FM1-43 at the mouse neuromuscular junction.

Results: Neither anesthetic evoked spontaneous exocytosis of synaptic vesicles, but both significantly inhibited the depolarization evoked by 4-aminopyridine and veratridine, suggesting a putative action on sodium channels. Exocytosis evoked by veratridine was inhibited by tetrodotoxin alone or in conjunction with sevoflurane or isoflurane, indicating that both agents may target voltage-gated sodium channels.

Conclusions: We suggest that sevoflurane and isoflurane inhibit exocytosis evoked by sodium-dependent depolarization and might act on tetrodotoxin-sensitive sodium channels. These findings contribute to a better understanding of some clinical neuromuscular effects induced by these anesthetics.

Keywords: FM1-43; exocytosis; isoflurane; neuromuscular junction; sevoflurane; synaptic vesicle.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Diaphragm / drug effects
  • Diaphragm / innervation
  • Diaphragm / physiology
  • Female
  • Isoflurane / pharmacology*
  • Methyl Ethers / pharmacology*
  • Mice
  • Neuromuscular Junction / drug effects*
  • Neuromuscular Junction / physiology
  • Presynaptic Terminals / drug effects*
  • Presynaptic Terminals / physiology
  • Sevoflurane

Substances

  • Anesthetics, Inhalation
  • Methyl Ethers
  • Sevoflurane
  • Isoflurane