{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:07:21Z","timestamp":1789945641468,"version":"4.0.1"},"reference-count":38,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,10,15]]},"abstract":"<jats:p>BmK I, a site-3-specific modulator of VGSCs (voltage-gated sodium channels) from the Chinese scorpion Buthus martensi Karsch, can induce spontaneous nociception and hyperalgesia and generate epileptiform responses in rats, which is attributed to the modulation of VGSCs in the neural system. However, which VGSC subtype is targeted by BmK I remains to be identified. Using two-electrode voltage-clamp recording, we studied the efficacy and selectivity of BmK I to three neuronal VGSCs co-expressed with the auxiliary \u03b21 subunit in Xenopus oocytes. Results revealed that BmK I induced a large increase in both transient and persistent currents in mNav1.6\u03b1\/\u03b21 (where m indicates mouse), which correlated with a prominent reduction in the fast component of inactivating current. In comparison, BmK I-increased currents of rNav1.2\u03b1\/\u03b21 (where r indicates rat) and rNav1.3\u03b1\/\u03b21 were much smaller. The EC50 values of BmK I for rNav1.2\u03b1\/\u03b21 (252\u00b160\u00a0nM) and mNav1.6\u03b1\/\u03b21 (214\u00b130\u00a0nM) were similar and roughly half of that for rNav1.3\u03b1\/\u03b21 (565\u00b116\u00a0nM). Moreover, BmK I only accelerated the slow inactivation development and delay recovery of mNav1.6\u03b1\/\u03b21 through binding to the channel in the open state. Residue-swap analysis verified that an acidic residue (e.g. Asp1602 in mNav1.6) within the domain IV S3\u2013S4 extracellular loop of VGSCs was crucial for the selectivity and modulation pattern of BmK I. Our findings thus provide the molecular determinant explaining the divergent and intriguing behaviour of neuronal VGSCs in response to site-3-specific modulators, indicating that these subtypes play different roles in BmK I-induced hyperexcitablity in rat models.<\/jats:p>","DOI":"10.1042\/bj20100517","type":"journal-article","created":{"date-parts":[[2010,8,3]],"date-time":"2010-08-03T13:23:03Z","timestamp":1280841783000},"page":"289-298","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Molecular determination of selectivity of the site 3 modulator (BmK I) to sodium channels in the CNS: a clue to the importance of Nav1.6 in BmK I-induced neuronal hyperexcitability"],"prefix":"10.1042","volume":"431","author":[{"given":"Huiqiong","family":"He","sequence":"first","affiliation":[{"name":"Graduate School of Chinese Academy of Sciences, Shanghai Institute of Physiology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhiRui","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200436, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangqian","family":"Dong","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200436, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200436, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200436, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Ji","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200436, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2010,9,28]]},"reference":[{"key":"2021112214381062500_B1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0896-6273(00)81133-2","article-title":"From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels","volume":"26","author":"Catterall","year":"2000","journal-title":"Neuron"},{"key":"2021112214381062500_B2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1242\/jeb.205.5.575","article-title":"Evolution of voltage-gated Na+ channels","volume":"205","author":"Goldin","year":"2002","journal-title":"J. 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