The activation effect of hainantoxin-I, a peptide toxin from the Chinese spider, Ornithoctonus hainana, on intermediate-conductance Ca2+-activated K+ channels.
The activation effect of hainantoxin-I, a peptide toxin from the Chinese spider, Ornithoctonus hainana, on intermediate-conductance Ca2+-activated K+ channels.
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海南蜘蛛肽毒素海南毒素-I 对中导 Ca2+ 激活 K 通道的激活作用
DOI：
10.3390/toxins6082568
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发表时间：
2014-08-21
期刊：
影响因子：
4.2
通讯作者：
Liang S
中科院分区：
文献类型：
--
作者：
Huang P;Zhang Y;Chen X;Zhu L;Yin D;Zeng X;Liang S
Intermediate-conductance Ca2+-activated K+ (IK) channels are calcium/calmodulin-regulated voltage-independent K+ channels. Activation of IK currents is important in vessel and respiratory tissues, rendering the channels potential drug targets. A variety of small organic molecules have been synthesized and found to be potent activators of IK channels. However, the poor selectivity of these molecules limits their therapeutic value. Venom-derived peptides usually block their targets with high specificity. Therefore, we searched for novel peptide activators of IK channels by testing a series of toxins from spiders. Using electrophysiological experiments, we identified hainantoxin-I (HNTX-I) as an IK-channel activator. HNTX-I has little effect on voltage-gated Na+ and Ca2+ channels from rat dorsal root ganglion neurons and on the heterologous expression of voltage-gated rapidly activating delayed rectifier K+ channels (human ether-à-go-go-related gene; human ERG) in HEK293T cells. Only 35.2% ± 0.4% of the currents were activated in SK channels, and there was no effect on BK channels. We demonstrated that HNTX-I was not a phrenic nerve conduction blocker or acutely toxic. This is believed to be the first report of a peptide activator effect on IK channels. Our study suggests that the activity and selectivity of HNTX-I on IK channels make HNTX-I a promising template for designing new drugs for cardiovascular diseases.
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影响因子：
16.6
作者：
通讯作者：
--
影响因子：
3.6
作者：
Cummins, TR;Aglieco, F;Dib-Hajj, SD
通讯作者：
Dib-Hajj, SD
DOI：
10.1073/pnas.1220253110
发表时间：
2013-03-19
影响因子：
11.1
作者：
Zhang, Miao;Pascal, John M.;Zhang, Ji-Fang
通讯作者：
Zhang, Ji-Fang
影响因子：
3.6
作者：
Bosmans, F;Rash, L;Tytgat, J
通讯作者：
Tytgat, J
影响因子：
3.5
作者：
Morimura, K;Yamamura, H;Imaizumi, Y
通讯作者：
Imaizumi, Y