Worm Breeder's Gazette 9(1): 45
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
The mechanism of action of volatile anesthetics is unknown. Since C. elegans has a relatively simple nervous system, we are using it to study the effect of anesthetics. We hope that by comparing N2 to other strains showing altered responses to anesthetics, we may be able to locate the locus of anesthetic action. N2 responds to anesthetics in a manner correlating well to more complex organisms. The anesthetics render nematodes immobile, and the effect is quickly reversible. We define anesthesia in N2 as immobility for longer than 10 seconds . The ED(50) is that 'effective dose ' or concentration which anesthetizes 50% of the individuals. When the log ED(50)'s of the different anesthetics are graphed versus the respective oil/gas partition coefficients (O/G ) one obtains a straight line with a slope of -1 in all other organisms studied. We found this to be true also in C. elegans. We have isolated a mutant, ec1, which shows an altered response to volatile anesthetics. The mutant shows increased sensitivity to some anesthetics, but not all. The slope of the log- log plot between the ED(50) 's and the O/G 's is altered. To our knowledge, this is the only organism for which this is true. We feel there is a good chance that the alteration is at the site of action of volatile anesthetics. Analsysis of ec1 shows that it does not complement unc-79. We therefore tested two other alleles of this gene and found that e1068 and e1291 are similarly altered in their response to anesthetics. We have also obtained a strain from Jim Lewis, unc-80, which shows sensitivities to anesthetics very similar to ec1. (Both unc-79 and unc-80 have a 'fainter' phenotype.) Using anesthetic hyper. sensitivity as a phenotype, we have mapped unc-80 to linkage group V. In addition, we have now isolated an X-linked suppressor mutation, itself Unc, that returns unc-80 and unc-1 to normal anesthetic sensitivities. This suppressor, a recessive mutation, has normal anesthetic sensitivity. We are continuing to map unc-80 and the suppressor. We are also constructing a double mutant unc-79;unc-80 to determine its response to anesthetics. In the long run, we would like to determine the molecular differences between N2, unc-79, and unc-8O.