Potentiation and inhibition of glycine receptors by tutin

摘要: In the present study we characterized effects of South American neurotoxin tutin on recombinant glycine receptors (GlyR) expressed in HEK 293 cells using whole-cell patch-clamp techniques. Tutin induced a concentration-dependent inhibition α(1) and α(2) homomeric GlyRs, with IC(50)s 35 ± 1 15 3 μM, respectively. The co-expression αβ subunits reduced potency tutin, thus increasing IC(50) to 51 4 41 8 μM for α(1)β α(2)β inhibitory effect was competitive, independent membrane potential reversible suggesting pore site. On other hand, low concentrations enhanced current, which not synergic Zn(2+) or ethanol. A mutation Lys385 altered ethanol but sensitivity, different sites modulation α1-containing GlyRs. Our results suggest that affects GlyR by mechanism distinct picrotoxin ethanol, pharmacological profile exhibits "Zn-like" behaviour. conclusion, these provide information molecular mechanisms important understanding toxic recently discovered neurotoxin.