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

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.