Synthetic undecapeptide (NTX10-20) of noxiustoxin blocks completely the I(A) potassium currents of cerebellum granular cells.
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 NTXI-20 and NTX1-9 had a half-effective dose IC50 of approximately 2 and 10 microM, respectively, which correlates with their biological effects in vivo. Synthetic peptide NTX10-20 was quite remarkable in having a preference for the IA current, which was completely inhibited at high peptide concentration. The effects of the other peptides (NTXI 14, NTX21-39 and NTX30-39), although positive and reversible, required higher concentrations (50 200 microM) 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.
Frau
A
A
Istituto di Cibernetica e Biofisica, CNR, Genoa, Italy.
Pisciotta
M
M
Gurrola
G B
GB
Possani
L D
LD
Prestipino
G
G
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010452:Peptide Biosynthesis; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000737:chemistry* / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid
D010455:Peptides; D026902:Potassium Channel Blockers; D012604:Scorpion Venoms; C052567:noxiustoxin; D011188:Potassium