Gap junction modulators for C. elegans

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Discussion Overview

The discussion centers on the search for gap junction modulators specific to C. elegans, particularly focusing on the effectiveness of known compounds and the potential use of RNA interference (RNAi) techniques. Participants explore the implications of using mutant strains and the challenges associated with identifying suitable modulators for innexin proteins.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • One participant inquires about known gap junction openers or closers for C. elegans, mentioning compounds like trimethylamine, quinine, and carbenoxolone, which are effective in mammals but may not work on innexin proteins.
  • Another participant suggests contacting principal investigators (PIs) for insights on the use of these drugs in C. elegans.
  • A participant raises the possibility of using RNAi, noting the requirement that the targeted gene must be solely involved in gap junctions.
  • Concerns are expressed about the presence of non-neuronal gap junctions and the complexity of inx gene expression across different cell types.
  • Discussion includes the association of unc genes with innexins, with a participant questioning the uniqueness of these genes in relation to gap junctions.

Areas of Agreement / Disagreement

Participants do not reach a consensus on the effectiveness of specific gap junction modulators or the feasibility of using RNAi techniques, indicating that multiple competing views and uncertainties remain in the discussion.

Contextual Notes

Limitations include the uncertainty regarding the specificity of inx genes to gap junctions and the potential impact of using mutant strains on experimental results.

Pythagorean
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Are there any known gap junction openers/closers for C. elegans? I've googled far and wide for weeks. Trimethylamine, quinine, and carbenoxolone are known to work with connexins in mammals. They also happen to be expensive and require more paperwork, so I don't want to go through the steps just to find they don't work on innexin proteins (inx genes).

There are mutant strains (in inx genes) of C. elegans, but gap junctions are important in development too, so I'd think using mutants would meddle with results when trying to assay the function of gap junctions in healthy adults.
 
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I don't know, you could contact some PIs and ask whether they have experience with the drugs.
 
Yeah, I suppose it's come down to that. Thanks for the reply.
 
Would RNAi work?

Take a look at http://www.jbc.org/content/281/12/7881.short Fig 4B. I believe the caveat is that it requires that the gene is involved only in gap junctions and no where else (ie. gap junction => gene, but I don't know if there is evidence that gene => gap junction).
 
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link didn't work for me. (edit: ok, nevermind worked the second try)

Another thing with RNAi is there are non-neuronal gap junctions. But there are several different inx genes associated with different sets of cells. I use wormweb to see what genes are expressed in what neuron, but I've never found a neuron of interest for which inx genes are uniquely expressed.
 
ah yes, that paper uses unc genes, which are associated with innexins, but I don't think it's unique. Some inx genes actually code for the subunits of the gap junction.

Anyway, I'll have to think about RNAi with inx genes more.