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The Activation Effect of Hainantoxin-I, a Peptide Toxin from the Chinese Spider, Ornithoctonus hainana, on Intermediate-Conductance Ca(2+)-Activated K(+) Channels

Intermediate-conductance Ca(2+)-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 syn...

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Detalles Bibliográficos
Autores principales: Huang, Pengfei, Zhang, Yiya, Chen, Xinyi, Zhu, Li, Yin, Dazhong, Zeng, Xiongzhi, Liang, Songping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147597/
https://www.ncbi.nlm.nih.gov/pubmed/25153257
http://dx.doi.org/10.3390/toxins6082568
Descripción
Sumario:Intermediate-conductance Ca(2+)-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 Ca(2+) 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.