IR@PKUHSC  > 北京大学第一临床医学院  > 皮肤性病科
学科主题临床医学
Temperature dependence of erythromelalgia mutation L858F in sodium channel Nav1.7
Han, Chongyang; Lampert, Angelika; Rush, Anthony M.; Dib-Hajj, Sulayman D.; Wang, Xiaoliang; Yang, Yong; Waxman, Stephen G.
刊名MOLECULAR PAIN
2007-01-19
DOI10.1186/1744-8069-3-3
3
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]CLOSED-STATE INACTIVATION ; SPINAL SENSORY NEURONS ; OF-FUNCTION MUTATION ; DORSAL-ROOT GANGLIA ; PARAMYOTONIA-CONGENITA ; NA+ CHANNEL ; ELECTROPHYSIOLOGICAL PROPERTIES ; BRUGADA-SYNDROME ; ALPHA-SUBUNIT ; PRIMARY ERYTHERMALGIA
英文摘要

Background: The disabling chronic pain syndrome erythromelalgia ( also termed erythermalgia) is characterized by attacks of burning pain in the extremities induced by warmth. Pharmacological treatment is often ineffective, but the pain can be alleviated by cooling of the limbs. Inherited erythromelalgia has recently been linked to mutations in the gene SCN9A, which encodes the voltage-gated sodium channel Nav1.7. Nav1.7 is preferentially expressed in most nociceptive DRG neurons and in sympathetic ganglion neurons. It has recently been shown that several disease-causing erythromelalgia mutations alter channel-gating behavior in a manner that increases DRG neuron excitability.

Results: Here we tested the effects of temperature on gating properties of wild type Nav1.7 and mutant L858F channels. Whole-cell voltage-clamp measurements on wild type or L858F channels expressed in HEK293 cells revealed that cooling decreases current density, slows deactivation and increases ramp currents for both mutant and wild type channels. However, cooling differentially shifts the midpoint of steady-state activation in a depolarizing direction for L858F but not for wild type channels.

Conclusion: The cooling-dependent shift of the activation midpoint of L858F to more positive potentials brings the threshold of activation of the mutant channels closer to that of wild type Nav1.7 at lower temperatures, and is likely to contribute to the alleviation of painful symptoms upon cooling in affected limbs in patients with this erythromelalgia mutation.

语种英语
WOS记录号WOS:000246353200001
Citation statistics
Cited Times:25[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65249
Collection北京大学第一临床医学院_皮肤性病科
作者单位1.Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China
2.Peking Union Med Coll, Beijing 100050, Peoples R China
3.Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA
4.Yale Univ, Sch Med, Ctr Neurosci & Regenerat Res, New Haven, CT 06510 USA
5.Vet Affairs Connecticut Healthcare Ctr, Rehabil Res Ctr, West Haven, CT 06516 USA
6.Peking Univ, First Hosp, Dept Dermatol, Beijing 100034, Peoples R China
7.NeuroSolut Ltd, Coventry CV4 7ZS, W Midlands, England
Recommended Citation
GB/T 7714
Han, Chongyang,Lampert, Angelika,Rush, Anthony M.,et al. Temperature dependence of erythromelalgia mutation L858F in sodium channel Nav1.7[J]. MOLECULAR PAIN,2007,3.
APA Han, Chongyang.,Lampert, Angelika.,Rush, Anthony M..,Dib-Hajj, Sulayman D..,Wang, Xiaoliang.,...&Waxman, Stephen G..(2007).Temperature dependence of erythromelalgia mutation L858F in sodium channel Nav1.7.MOLECULAR PAIN,3.
MLA Han, Chongyang,et al."Temperature dependence of erythromelalgia mutation L858F in sodium channel Nav1.7".MOLECULAR PAIN 3(2007).
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