{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T13:48:58Z","timestamp":1762955338785,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T00:00:00Z","timestamp":1408579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"National 973 Project of China","award":["2010CB529800","2012CB22305"],"award-info":[{"award-number":["2010CB529800","2012CB22305"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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-\u00e0-go-go-related gene; human ERG) in HEK293T cells. Only 35.2% \u00b1 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.<\/jats:p>","DOI":"10.3390\/toxins6082568","type":"journal-article","created":{"date-parts":[[2014,8,21]],"date-time":"2014-08-21T11:00:23Z","timestamp":1408618823000},"page":"2568-2579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Activation Effect of Hainantoxin-I, a Peptide Toxin from the Chinese Spider, Ornithoctonus hainana, on Intermediate-Conductance Ca2+-Activated K+ Channels"],"prefix":"10.3390","volume":"6","author":[{"given":"Pengfei","family":"Huang","sequence":"first","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiya","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dazhong","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiongzhi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songping","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1124\/pr.57.4.9","article-title":"International union of pharmacology. 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