Tail clamp responses in stomatin knockout mice compared with mobility assays in Caenorhabditis elegans during exposure to diethyl ether, halothane, and isoflurane.
BACKGROUND
The gene unc-1 plays a central role in determining volatile anesthetic sensitivity in Caenorhabditis elegans. Because different unc-1 alleles cause strikingly different phenotypes in different volatile anesthetics, the UNC-1 protein is a candidate to directly interact with volatile anesthetics. UNC-1 is a close homologue of the mammalian protein stomatin, for which a mouse knockout was recently constructed. Because the stomatin gene is expressed in dorsal root ganglion cells, the authors hypothesized that the knockout would have an effect on anesthetic sensitivity in mice similar to that seen in nematodes.


METHODS
Mice were placed in semiclosed chambers and exposed to continuous flows of diethyl ether, halothane, or isoflurane in air. Using lack of response to tail clamp as an endpoint, the authors determined the EC50s for the knockout strain compared with the nonmutated parental strain. They compared the differences seen in the mouse strains with the differences seen in the nematode strains.


RESULTS
Stomatin-deficient mice had a 12% increase in sensitivity to diethyl ether but no significant change in sensitivity to halothane or isoflurane compared with wild type. No defect in locomotion was noted in the mutant mouse.


CONCLUSIONS
Nematodes and mice with deletions of the stomatin gene both have increased sensitivity to diethyl ether. Neither nematodes nor mice with stomatin deficiencies have significantly altered sensitivity to isoflurane or halothane. The effects of stomatin deficiency cross phylogenetic boundaries and support the importance of this protein in anesthetic response and the use of C. elegans as a model for anesthetic action in mammals.
Sedensky
Margaret M
MM
Department of Anesthesiology, University Hospitals of Cleveland and Case School of Medicine, Cleveland, Ohio 44106-507, USA.
Pujazon
Melissa A
MA
Morgan
Phil G
PG
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology; D004986:Ether / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009068:Movement
D018685:Anesthetics, Inhalation; D001798:Blood Proteins; C488964:Stom protein, mouse; D008565:Membrane Proteins; D004986:Ether; D007530:Isoflurane; D006221:Halothane