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.

Do Nematodes Sleep Around Under the Influence of Drugs?

P. Morgan, M. Sedensky, and P. Meneely

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.