A positive charge at the N-terminal segment of Discrepin increases the blocking effect of K⁺ channels responsible for the I_A currents in cerebellum granular cells

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• 作者：Stefania Romeo ; Gerardo Corzo ; Attilio Vasile ; Honoo Satake ; Gianfranco Prestipino ; Lourival D. Possani
• 关键词：A-currents ; Discrepin ; K⁺ channel ; Structure-function ; Scorpion toxin
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：2008
• 出版时间：April 2008
• 年：2008
• 卷：1780
• 期：4
• 页码：750-755
• 全文大小：475 K

文摘

Discrepin is a scorpion peptide that blocks preferentially the I_A currents of the voltage-dependent K⁺ channel of rat cerebellum granular cells. It was isolated from the venom of the buthid scorpion Tityus discrepans and contains 38 amino acid residues with a pyroglutamic acid at the N-terminal site. Discrepin has the lowest sequence identity (approx. 50 % ) among the six members of the -KTx15 sub-family of scorpion toxins. In order to find out which residues are important for the blocking effects of Discrepin, six mutants were chemically synthesized (V6K, I19R, D20K, T35V, I19R-D20K, I19R-D20K-R21V), correctly folded and their physiological properties were examined. Substitution of residues V6 and D20 for basically charged amino acids increases the blocking activity of Discrepin, specially the mutation V6K at the N-terminal segment of the toxin. Analysis of 3D-structure models of the mutants V6K and D20K supports the idea that basic residues improve their blocking activities, similarly to what happens with BmTx3, a toxic peptide obtained from Buthus martensi scorpion, which has the highest known blocking effects of I_A currents in K⁺ channels of rat cerebellum granular cells.