Synthetic undecapeptide (NTX10–20) of noxiustoxin blocks completely the I _A potassium currents of cerebellum granular cells

Abstract.

Native noxiustoxin (NTX) and synthetic peptides corresponding to its primary sequence, from positions 1–9, 1–14, 1–20, 10–20, 21–39 and 30–39, were prepared and assayed on the K⁺ currents of cerebellum granular cells, using the patch-clamp technique in the whole-cell configuration system. Native toxin has a reversible inhibitory effect (IC₅₀=360 nM), whereas synthetic peptides NTX1–20 and NTX1–9 had a half-effective dose IC₅₀ of approximately 2 and 10 µM, respectively, which correlates with their biological effects in vivo. Synthetic peptide NTX10–20 was quite remarkable in having a preference for the I _A current, which was completely inhibited at high peptide concentration. The effects of the other peptides (NTX1–14, NTX21–39 and NTX30–39), although positive and reversible, required higher concentrations (50–200 µM) to block both currents, suggesting no affinity or, at least, much lower specificity for the channels responsible for the potassium currents in the granular cells studied.