Electrophysiological Characterization of Ts6 and Ts7, K+ Channel Toxins Isolated through an Improved Tityus serrulatus Venom Purification Procedure

Toxins

Felipe A. Cerni²  Manuela B. Pucca²  Steve Peigneur¹  Caroline M. Cremonez²  Karla C. F. Bordon²  Jan Tytgat¹ 

[1] Toxicology and Pharmacology, University of Leuven, O&N 2, Herestraat 49, P.O. Box 922, Leuven 3000, Belgium; E-Mails:;Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café, s/n, 14040-903, Ribeirão Preto, SP, Brazil; E-Mails:

关键词: Tityus serrulatus;    neurotoxins;    potassium channels;    α-KTx;    scorpion venom;   

DOI  :  10.3390/toxins6030892

来源: mdpi

【 摘 要 】

In Brazil, Tityus serrulatus (Ts) is the species responsible for most of the scorpion related accidents. Among the Ts toxins, the neurotoxins with action on potassium channels (α-KTx) present high interest, due to their effect in the envenoming process and the ion channel specificity they display. The α-KTx toxins family is the most relevant because its toxins can be used as therapeutic tools for specific target cells. The improved isolation method provided toxins with high resolution, obtaining pure Ts6 and Ts7 in two chromatographic steps. The effects of Ts6 and Ts7 toxins were evaluated in 14 different types of potassium channels using the voltage-clamp technique with two-microelectrodes. Ts6 toxin shows high affinity for Kv1.2, Kv1.3 and Shaker IR, blocking these channels in low concentrations. Moreover, Ts6 blocks the Kv1.3 channel in picomolar concentrations with an IC₅₀ of 0.55 nM and therefore could be of valuable assistance to further designing immunosuppressive therapeutics. Ts7 toxin blocks multiple subtypes channels, showing low selectivity among the channels analyzed. This work also stands out in its attempt to elucidate the residues important for interacting with each channel and, in the near future, to model a desired drug.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.