Worm Breeder's Gazette 11(2): 87

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.

A kra-1 Gene Might Encode a Nicotinic Receptor-Associated NMDA Type Ion Channel in C. elegans

Hideki Ando and Hiroaki Kagawa

Figure 1

Recent studies in invertebrate glutamate receptors indicate the 
presence of at least three types of glutamate receptors, none of which 
are of the NMDA type.  Pharmacological data have shown invertebrate 
glutamate receptor ion channels have less selectivity for 
noncompetitive antagonists than that of NMDA receptor ion channels and 
are not shared a voltage-sensitive block by Mg2+ ions, a property of 
NMDA receptor ion channel.  We have tested pharmacological effect of 
noncompetitive antagonist of NMDA receptors to the worm.  In 
competition assay using cut worm bathing in drug solution, nicotinic 
transmission appeared to be specifically antagonized by ketamine, a 
non-competitive antagonist of NMDA receptor.  We have isolated sixteen 
EMS induced mutants showing convulsions against 30mM ketamine and 
other NMDA noncompetitive antagonists; 1mM PCP and MK-801.  In the 
case of cut worm assay, convulsion could be induced at less than one 
tenth concentrations.  Genetic study to one strain kh30 identified a 
gene kra-1 which was mapped on the locus closed to mec-1 and unc-68 
loci on chromosome V.  kra-1(kh30) animal was weak resistant to 
nicotine (0.1mM), suggesting this convulsion was derived from 
defective function of nicotine receptor system.  Defective site of kra-
1(kh30) might be on nicotinic receptor-associated ion channel because 
kra-1(kh30) was also weak resistant to channel activator ouabine (0.
1mM).  Competitive nicotinic antagonist d-tubocuraine suppressed 
ketamine function to kra-1(kh30) animal.  This suggests that binding 
affinity of ketamine to ion channel decreased in inactivated state.  
Finally, convulsion expression of kra-1(kh30) animal with ketamine was 
also suppressed by Mg2+ ion.  These data permit us to conclude that 
this ion channel could be associated by nicotinic receptor with 
pharmacological homology to vertebrate NMDA ion channel.  Cloning and 
molecular study of the gene will confirm a pharmacological results.
[See Figure 1]

Figure 1