Escoubas Pierre, Diochot Sylvie, Célérier Marie-Louise, Nakajima Terumi, Lazdunski Michel
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique-Unité Mixte Recherche 6097, Sophia-Antipolis, Valbonne, France.
Mol Pharmacol. 2002 Jul;62(1):48-57. doi: 10.1124/mol.62.1.48.
Three novel peptides with the ability to inhibit voltage-dependent potassium channels in the shab (Kv2) and shal (Kv4) subfamilies were identified from the venom of the African tarantulas Stromatopelma calceata (ScTx1) and Heteroscodra maculata (HmTx1, HmTx2). The three toxins are 34- to 38-amino acid peptides that belong to the structural family of inhibitor cystine knot spider peptides reticulated by three disulfide bridges. Electrophysiological recordings in COS cells show that these toxins act as gating modifier of voltage-dependent K+ channels. ScTx1 is the first high-affinity inhibitor of the Kv2.2 channel subtype (IC50, 21.4 nM) to be described. ScTx1 also inhibits the Kv2.1 channels, with an IC50 of 12.7 nM, and Kv2.1/Kv9.3 heteromultimers that have been proposed to be involved in O2 sensing in pulmonary artery myocytes. In addition, it is the most effective inhibitor of Kv4.2 channels described thus far, with an IC50 of 1.2 nM. HmTx toxins share sequence similarities with both the potassium channel blocker toxins (HmTx1) and the calcium channel blocker toxin omega-GsTx SIA (HmTx2). They inhibit potassium current associated with Kv2 subtypes in the 100 to 300 nM concentration range. HmTx2 seems to be a specific inhibitor of Kv2 channels, whereas HmTx1 also inhibits Kv4 channels, including Kv4.1, with the same potency. HmTx1 is the first described peptide effector of the Kv4.1 subtype. Those novel toxins are new tools for the investigation of the physiological role of the different potassium channel subunits in cellular physiology.
从非洲狼蛛Stromatopelma calceata（ScTx1）和Heteroscodra maculata（HmTx1、HmTx2）的毒液中鉴定出三种具有抑制shab（Kv2）和shal（Kv4）亚家族电压依赖性钾通道能力的新型肽。这三种毒素是由34至38个氨基酸组成的肽，属于由三个二硫键交联的抑制性胱氨酸结蜘蛛肽结构家族。在COS细胞中的电生理记录表明，这些毒素作为电压依赖性K+通道的门控修饰剂发挥作用。ScTx1是所描述的Kv2.2通道亚型的首个高亲和力抑制剂（IC50为21.4 nM）。ScTx1还抑制Kv2.1通道，IC50为12.7 nM，并且抑制Kv2.1/Kv9.3异源多聚体，后者被认为参与肺动脉肌细胞中的氧传感。此外，它是迄今为止所描述的Kv4.2通道最有效的抑制剂，IC50为1.2 nM。HmTx毒素与钾通道阻断毒素（HmTx1）和钙通道阻断毒素ω-GsTx SIA（HmTx2）均具有序列相似性。它们在100至300 nM浓度范围内抑制与Kv2亚型相关的钾电流。HmTx2似乎是Kv2通道的特异性抑制剂，而HmTx1也以相同效力抑制包括Kv4.1在内的Kv4通道。HmTx1是所描述的Kv4.1亚型的首个肽效应物。这些新型毒素是研究不同钾通道亚基在细胞生理学中的生理作用的新工具。
