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The effect of spider toxin PhTx3-4, ω-conotoxins MVIIA and MVIIC on glutamate uptake and on capsaicin-induced glutamate release and [Ca2+]i in spinal cord synaptosomes. | LitMetric

AI Article Synopsis

  • PhTx3-4, a spider toxin, inhibits both calcium-dependent and calcium-independent release of glutamate in spinal cord synaptosomes, while conus toxins only affect calcium-dependent release.
  • PhTx3-4 uniquely inhibits glutamate uptake by synaptosomes, leading to reduced calcium-independent glutamate release, a property not seen in other known polypeptide toxins.
  • Both PhTx3-4 and conus toxins are blockers of voltage-dependent calcium channels and significantly reduce the rise in intracellular calcium levels induced by capsaicin, suggesting potential therapeutic uses for PhTx3-4 in treating abnormal glutamate release during pathological conditions like pain.

Article Abstract

In spinal cord synaptosomes, the spider toxin PhTx3-4 inhibited capsaicin-stimulated release of glutamate in both calcium-dependent and -independent manners. In contrast, the conus toxins, ω-conotoxin MVIIA and xconotoxin MVIIC, only inhibited calcium-dependent glutamate release. PhTx3-4, but not ω-conotoxin MVIIA or xconotoxin MVIIC, is able to inhibit the uptake of glutamate by synaptosomes, and this inhibition in turn leads to a decrease in the Ca(2+)-independent release of glutamate. No other polypeptide toxin so far described has this effect. PhTx3-4 and ω-conotoxins MVIIC and MVIIA are blockers of voltage-dependent calcium channels, and they significantly inhibited the capsaicin-induced rise of intracellular calcium [Ca(2+)](i) in spinal cord synaptosomes, which likely reflects calcium entry through voltage-gated calcium channels. The inhibition of the calcium-independent glutamate release by PhTx3-4 suggests a potential use of the toxin to block abnormal glutamate release in pathological conditions such as pain.

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Source
http://dx.doi.org/10.1007/s10571-010-9618-5DOI Listing

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