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The Activation Effect of Hainantoxin-I, a Peptide Toxin from the Chinese Spider, Ornithoctonus hainana, on Intermediate-Conductance Ca2+-Activated K+ Channels
- Source :
- Toxins, Vol 6, Iss 8, Pp 2568-2579 (2014)
- Publication Year :
- 2014
- Publisher :
- MDPI AG, 2014.
-
Abstract
- 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.
- Subjects :
- IK channels
peptide activator
HNTX-I
selectivity
new drug design
Medicine
Subjects
Details
- Language :
- English
- ISSN :
- 20726651
- Volume :
- 6
- Issue :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- Toxins
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5a2da890aaa84f2d90860b5fcd7394ef
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/toxins6082568