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It has been thought that the high pressures of helium and neon that might be needed to produce anesthesia antagonize their anesthetic properties (pressure reversal of anesthesia). We propose an alternative explanation: like other compounds with a low affinity to water, helium and neon are intrinsically without anesthetic effect.

Laboratory mouse strains differ significantly in susceptibility to anesthetics. These phenotypic differences may be exploited to help determine the genetic basis of anesthetic-induced immobility.

Anesthetic potency differs by modest amounts among inbred, outbred, wild, and laboratory mouse strains. Absence of the neural form of protein kinase C increases minimum alveolar anesthetic concentration for isoflurane, indicating that protein phosphorylation by the gamma-isoform of protein kinase C (PKCgamma) can influence the potency of this anesthetic.

Glycine receptors (GlyRs) are pentameric ligand-gated ion channels that mediate inhibitory neurotransmission in the brain and spinal cord and are targets of alcohols and anesthetics. The transmembrane (TM) domain of GlyR subunits is composed of four α-helical segments (TM1–4), but there are conflicting data about the orientation of TM3 and TM4 and, therefore, also the proximity of residues (e.g., A288) that are important for alcohol and anesthetic effects. In the present study, we investigated the proximity of A288 in TM3 to residues in TM4 from M404 to K411. We generated eight double mutant GlyRs (A288C/M404C, A288C/F405C, A288C/Y406C, A288C/W407C, A288C/I408C, A288C/I409C, A288C/Y410C, and A288C/K411C), as well as the corresponding single mutants, and expressed them in Xenopus laevis oocytes. To measure glycine responses, we used two-electrode voltage clamp electrophysiology. We built homology models of the GlyR using structures of the nicotinic acetylcholine receptor (nAChR) and a prokaryotic ion channel (Gloeobacter violaceus, GLIC) as templates, and asked which model best fit our experimental data. Application of the cross-linking reagent HgCl2 in the closed state produced a leftward shift in the glycine concentration–response curves of the A288C/W407C and A288C/Y410C mutants, suggesting they are able to form cross-links. In addition, when HgCl2 was coapplied with glycine, responses were changed in the A288C/Y406C, A288C/I409C, and A288C/Y410C double mutants, suggesting that agonist-induced rotation of TM4 allows A288C/Y406C and A288C/I409C to cross-link. These results are consistent with a model of GlyR, based on nAChR, in which A288, Y406, W407, I409, and Y410 face into a four-helical bundle.

Regardless of the duration of anesthesia, elimination is faster and recovery is quicker for the inhaled anesthetic desflurane than for the inhaled anesthetic sevoflurane. The toxic degradation product of sevoflurane, Compound A, seems to bind irreversibly to proteins in the body.

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