CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is a selective blocker of L-type calcium channels in mammalian neurons
CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is a selective blocker of L-type calcium channels in mammalian neurons
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DOI：
10.1016/j.neuropharm.2007.03.012
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发表时间：
2007-06-01
影响因子：
4.7
通讯作者：
Kuhn-Nentwig, Lucia
中科院分区：
文献类型：
--
作者：
Kubista, Helmut;Mafra, Roberta A.;Kuhn-Nentwig, Lucia
在 Cupiennius salei 毒液的 CSTX-1 结构中鉴定出的抑制剂胱氨酸结基序表明，这种毒素可能充当离子通道的阻断剂。对蟑螂神经元进行的全细胞膜片钳实验表明，CSTX-1 对中/低电压 (M-LVA) 和高电压激活 (HVA) 昆虫 Ca-v 通道产生缓慢的电压无关阻断。由于 C. salei 毒液影响昆虫和啮齿类动物，我们研究了大鼠神经元的 Ca-v 通道电流是否也被 CSTX-1 抑制。 CSTX-1阻断大鼠神经元L型通道，但不阻断其他类型的HVA Ca-v通道，并且不能调节LVA Ca-v通道电流。使用神经内分泌 GH3 和 GH4 细胞，CSTX-1 产生快速、电压无关的 L 型 Cav 通道电流阻断。 GH4 神经元中的浓度-反应曲线是双相的，亚纳摩尔 IC50 值比 GH3 细胞中至少低 1000 倍。骨骼肌肌球的L型Ca-v通道电流和大鼠神经元的其他电压门控离子电流，例如I-Na(v)或I-K(v)不受CSTX-1影响。 CSTX-1 对哺乳动物神经元中 L 型 Ca-v 通道子集的高效力和选择性可能使该毒素能够用作研究该 Cav 通道家族的分子工具。 (c) 2007 Elsevier Ltd. 保留所有权利。
The inhibitor cystine-knot motif identified in the structure of CSTX-1 from Cupiennius salei venom suggests that this toxin may act as a blocker of ion channels. Whole-cell patch-clamp experiments performed on cockroach neurons revealed that CSTX-1 produced a slow voltage-independent block of both mid/low- (M-LVA) and high-voltage-activated (HVA) insect Ca-v channels. Since C. salei venom affects both insect as well as rodent species, we investigated whether Ca-v channel currents of rat neurons are also inhibited by CSTX-1. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Ca-v channels, and failed to modulate LVA Ca-v channel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Cav channel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC50 values were at least 1000-fold lower than in GH3 cells. L-type Ca-v channel currents of skeletal muscle myoballs and other voltage-gated ion currents of rat neurons, such as I-Na(v) or I-K(v) were not affected by CSTX-1. The high potency and selectivity of CSTX-1 for a subset of L-type Ca-v channels in mammalian neurons may enable the toxin to be used as a molecular tool for the investigation of this family of Cav channels. (c) 2007 Elsevier Ltd. All rights reserved.