Modulation of a voltage-gated Na⁺channel by sevoflurane involves multiple sites and distinct mechanisms

Significance Understanding of the mechanisms of modulation of voltage-gated Na + (Na V ) channels by general anesthetic agents such as sevoflurane is critical to interpret their role in general anesthesia. By using the bacterial Na V channel analogue NaChBac plus a combination of computational and electrophysiological analyses, this work strongly suggests a multisite mechanism of sevoflurane action on Na V channels. Furthermore, computer simulations suggest specific putative anesthetic sites worthy of further investigation.