Hello everyone! I wanted to test some mutant worms on changes in their neurotransmission and i used time dependent aldicarb (an acetylcholine esterase inhibitor)
and PTZ (a GABA receptor agonist) assays as described by Locke 2008 (Paradigms for Pharmacological Characterization of C. elegans Synaptic Transmission Mutants).
My mutants did not display any phenotypes in the presence of PTZ but were aldicarb hypersensitive. According to the paper by Locke this means that they fail in the
negative regulation of acetylcholine (they should have more acetylcholine in their synapses). I then performed levamisole (competes with acetylcholine for the receptors)
assays. However, in this assays it seems that the mutants are responding similar to the wild type. I was expecting them to be more resistant, since they should have
more acetylcholine. Now I’m not sure what conclusions i could draw from those assays and all the papers that i read so far were not very illuminating for this problem.
Maybe someone can help me or has some ideas? That would be great.
If your worms are aldicarb hypersensitive, this suggests that they either 1) release more acetylcholine, 2) have more excitable muscle cells, or (maybe) 3) have defective inhibitory input to muscles (defective GABA). You’ve ruled out #3 as there is no difference in PTZ. Levamisole activates a subset of AChRs at the NMJ to paralyse the worm, so by observing no difference between wild type and mutant in the levamisole assay, the likelihood is that option #1 is correct, and your worms have more ACh release.
Thank you so much, that was extremely helpful! I was not aware, that levamisole goes to specific receptors, but now I have seen a paper describing it.
I’m so glad, that my results actually could make sense!