>>Now, a selfish question: Do you know of any spider toxins that
>specifically target GABA-A receptors?
So far, the GABA receptors have eluded me, though not for lack of trying ...
I have only had one customer who was willing and able to screen a large
variety of venoms against these receptors:
Schaeffer JM, Bergstrom AR (Life Sci 1988;43(21):1701-6) Identification of
gamma-aminobutyric acid and its binding sites in Caenorhabditis elegans.
In a screen of only 13 spider venoms, they found that Calilena spp.
(Agelenidae) venom blocks C. elegans GABA receptors with a KI of 6 nl(crude
venom) per milliliter. I do not think that the toxin was ever purified.
GABA receptors should be attractive targets for spider venoms and we do have
evidence that the venoms are targeting inhibitory synapses: At one time
Novascreen found a chloride channel antagonist in the venom of the scorpion,
Vejovis spinigerus, but I do not which chloride channel they used. Also,
Omega-agatoxin-IVA blocks the release of GABA (via modulation of GABAB
receptors via calcium channels) and arginine polyamine, an analogue of FTX
(Funnel Spider Toxin), blocks calcium dependent chloride channels.
GABA is also present in fairly high concentrations in some spider venoms and
it would be interesting to find out whether it functions like glutamate in
some venoms: polyamine toxins typically only block open channels and many
spider venoms appear to include high concentrations of glutamate to open
glutamate receptors. Of course, this also means that the screens might not
be very easy ... high concentrations of GABA will probably produce many
false leads and GABA can be difficult to separate from the proteins.
P.S. Thanks for feedback on the idea. Good to know that I haven't flipped