Role of Voltage-Gated Sodium Channels in the Mechanism of Ether-Induced Unconsciousness

Despite continuous clinical use for more than 170 years, the mechanism of general anesthetics has not been completely characterized. In this review, we focus on the role of voltage-gated sodium channels in the sedative–hypnotic actions of halogenated ethers, describing the history of anesthetic mechanisms research, the basic neurobiology and pharmacology of voltage-gated sodium channels, and the evidence for a mechanistic interaction between halogenated ethers and sodium channels in the induction of unconsciousness. We conclude with a more integrative perspective of how voltage-gated sodium channels might provide a critical link between molecular actions of the halogenated ethers and the more distributed network-level effects associated with the anesthetized state across species.