Differential sensitivity of sodium channels from the central and peripheral nervous system to the scorpion toxins Lqh-2 and Lqh-3
Differential sensitivity of sodium channels from the central and peripheral nervous system to the scorpion toxins Lqh-2 and Lqh-3
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DOI：
10.1046/j.1460-9568.2002.02142.x
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发表时间：
2002-08-01
影响因子：
3.4
通讯作者：
Heinemann, SH
中科院分区：
文献类型：
--
作者：
Chen, HJ;Lu, SQ;Heinemann, SH
从以色列黄蝎Leiurus quinquestriatus hebraeus的毒液中分离的蝎α毒素Lqh-2和Lqh-3先前显示在消除大鼠骨骼肌钠通道的快速失活方面非常有效（Chen等人，2000）。在这里，我们表明，河豚毒素敏感的神经元通道Na（V）1.2和Na（V）1.7，这主要是在哺乳动物的中枢和外周神经系统，分别表达，这两种毒素的敏感性差异。用膜片钳方法研究了rNa（V）1.2和hNa（V）1.7通道在哺乳动物细胞中表达后的变化。虽然Lqh-3在去除hNa（V）1.7通道中的失活方面比rNa（V）1.2强约100倍，但Lqh-2在另一个方向上的活性强约20倍。定点诱变表明，这些毒素的推定结合位点的差异，结构域4的S3-4接头，是Lqh-3的主要重要性，但不是Lqh-2。
The scorpion alpha-toxins Lqh-2 and Lqh-3, isolated from the venom of the Israeli yellow scorpion Leiurus quinquestriatus hebraeus , were previously shown to be very potent in removing fast inactivation of rat skeletal muscle sodium channels (Chen et al. , 2000). Here, we show that tetrodotoxin-sensitive neuronal channels Na(V)1.2 and Na(V)1.7, which are mainly expressed in mammalian central and peripheral nervous systems, respectively, are differentially sensitive to these two toxins. rNa(V)1.2 and hNa(V)1.7 channels were studied with patch-clamp methods upon expression in mammalian cells. While Lqh-3 was about 100-times more potent in removing inactivation in hNa(V) 1.7 channels compared with rNa(V) 1.2, Lqh-2 was about 20-times more active in the other direction. Site-directed mutagenesis showed that the differences in the putative binding sites for these toxins, the S3-4 linkers of domain 4, are of major importance for Lqh-3, but not for Lqh-2.