Common genetic determinants of halothane and isoflurane potencies in Caenorhabditis elegans

Background: Genetics provides a may to evaluate anesthetic action simultane ously at the molecular and behavioral levels. Results from strains that dif fer in anesthetic sensitivity have been mixed in their support of unitary t heories of anesthesia. Here the authors use the previously demonstrated lar ge variation of halothane sensitivities in Caenorhabditis elegans recombina nt inbred strains to assess the similarities of the determinants of halotha ne action with those of another volatile anesthetic, Isoflurane, Methods: The recombinant inbred strains, constructed from two evolutionaril y distinct C elegans lineages, were phenotyped. A coordination assay on aga r quantified the sensitivity to the volatile anesthetics; median effective concentrations (EC(50)s) were calculated by nonlinear regression of concent ration-response data and were correlated between the drugs for those strain s tested in common. Genetic loci were identified by statistical association between EC(50)s and chromosomal markers. Results: The recombinant inbred strains varied dramatically in sensitivity to halothane and isoflurane, with a 10-fold range in EC(50)s, Heritability estimates for each drug were imprecise but altogether high ( 49-80%). Halot hane and isoflurane EC(50)s were significantly correlated (r = 0.71, P < 10 (-9)). Genetic loci controlling sensitivity were found for both volatile an esthetics; the most significant determinant colocalized on chromosome V, A smaller recombinant inbred strain study of ethanol-induced immobility segre gated different genetic effects that did not correlate with sensitivity to either halothane or isoflurane, Conclusions: The genetic determinants driving the large variation in anesth etic sensitivity in these C elegans recombinant inbred strains are very sim ilar for halothane and isoflurane sensitivity.