Molecular determination of selectivity of the site 3 modulator (bmk i) to sodium channels in the cns: a clue to the importance of na(v)1.6 in bmk i-induced neuronal hyperexcitability
文献类型：期刊论文
| 作者 | He, Huiqiong2; Liu, ZhiRui1; Dong, Bangqian1; Zhou, Jingjing1; Zhu, Hongyan1; Ji, Yonghua1 |
| 刊名 | Biochemical journal
 |
| 出版日期 | 2010-10-15 |
| 卷号 | 431页码:289-298 |
| 关键词 | Alpha-like scorpion toxin Bmk i Fast inactivation Persistent current Slow inactivation Sodium channel |
| ISSN号 | 0264-6021 |
| DOI | 10.1042/bj20100517 |
| 通讯作者 | Ji, yonghua() |
| 英文摘要 | Bmk i. a site-3-specific modulator of vgscs (voltage-gated sodium channels) from the chinese scorpion blain's martens' 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 p i subunit in xenopus oocytes results revealed that bmk i induced a lame increase in both transient and persistent currents in mna(v)1.6 alpha/beta 1 (where in indicates mouse), which correlated with a prominent reduction in the fast component of in current in comparison, bmk i-increased currents of rna(v) 1 2 alpha/beta 1 (where r indicates rat) and rna(v)1.3 alpha/beta 1 were much smaller. the ec50 values of bmk i for rna(v) 1 2 alpha/beta 1 (252 +/- 6(1 nm) and mna, 1 6 alpha/beta 1 (214 +/- 30 nm) were similar and roughly half of that for rnav 1 3 alpha/beta 1 (565 +/- 16 nm) moreover, bmk i only accelerated the slow inactivation development and delay recovery of mna, 1.6 alpha/beta 1 through binding to the channel in the open state residue-swap analysis verified that an acidic residue (c asp(1602) in mna(v)1 6) within the domain iv s3-s4 extracellular loop of vgscs was crucial for the selectivity and modulation pattern of bmk 1 our findings thus provide the molecular determinant explaining the divergent and intringuing 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 |
| WOS关键词 | BUTHUS-MARTENSI KARSCH ; ALPHA-SCORPION TOXIN ; GATED NA+ CHANNELS ; SLOW INACTIVATION ; FUNCTIONAL-ANALYSIS ; RECEPTOR-SITE ; SPINAL-CORD ; BINDING ; EXPRESSION ; NEUROTOXIN |
| WOS研究方向 | Biochemistry & Molecular Biology |
| WOS类目 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000283378700013 |
| 出版者 | PORTLAND PRESS LTD |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2407172 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Ji, Yonghua |
| 作者单位 | 1.Shanghai Univ, Lab Neuropharmacol & Neurotoxicol, Shanghai 200436, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Physiol, Grad Sch, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Huiqiong,Liu, ZhiRui,Dong, Bangqian,et al. Molecular determination of selectivity of the site 3 modulator (bmk i) to sodium channels in the cns: a clue to the importance of na(v)1.6 in bmk i-induced neuronal hyperexcitability[J]. Biochemical journal,2010,431:289-298. |
| APA | He, Huiqiong,Liu, ZhiRui,Dong, Bangqian,Zhou, Jingjing,Zhu, Hongyan,&Ji, Yonghua.(2010).Molecular determination of selectivity of the site 3 modulator (bmk i) to sodium channels in the cns: a clue to the importance of na(v)1.6 in bmk i-induced neuronal hyperexcitability.Biochemical journal,431,289-298. |
| MLA | He, Huiqiong,et al."Molecular determination of selectivity of the site 3 modulator (bmk i) to sodium channels in the cns: a clue to the importance of na(v)1.6 in bmk i-induced neuronal hyperexcitability".Biochemical journal 431(2010):289-298. |
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来源：中国科学院大学
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