Mechanism of expression of voltage-gated sodium and calcium channels

电压门控钠通道和钙通道的表达机制

• 批准号: 16390056
• 负责人: OKAMURA Yasushi
• 金额: $ 7.3万
• 依托单位: National Institute of Natural Sciences Okazaki Research Facilities
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390056/
• 关键词: ion channel; voltage sensor; inactivation; persistent sodium current; sodium channel; ankyrin; PTEN; phosphatase

Ankyrin-G, a modular protein, plays a critical role in clustering voltage-gated sodium channels (Nav channels) in nodes of Ranvier and initial segments of mammalian neurons. However, direct effects of ankyrin-G on electrophysiological properties of Nav channels remai elusive. In this study, we explored whether ankyrin-G has a role in modifying gating properties of the neuronal Nav1.6 channel that is predominantly localized at nodes of Ranvier and initial segments. TsA201 cells transfected with the human Nav1.6 cDNA alone exhibited significant persistent sodium current (Ina-p). On the other hand, Ina-p was barely detected upon co-expression with ankyrin-G. Ankyrin-B, another ankyrin, did not show such an effect. Expression of chimeras between the two isofrms of ankyrin suggests that the membrane-binding domain of ankyurin-G is critical for reducing the Ina-p of Nav1.6. These results suggest that ankyrin-G regulates neuronal excitability not only through clustering Nav channels but also … More by directly modifying their channel gating. Changes is membraine potential affect ion channels, and transporters, which then alter intracellular chemical conditions. Ohter signaling pathways coupled to membrane potential have been suggested but their underlying mechanism are unknown. We have identified a novel protein from the ascidian Ciona intestinalis which has a transmembrane voltage sensing domain homologous to the S1-S4 segments of voltage-gated channels and a cytoplasmic domain similar to phosphatase and tension homologue (PTEN). This protein, named Ci-VSP (voltage-sensor containing phosphatase), displays channel-like "gating" currents and directly translates changes in membrane potential into the turnover of phosphoinositides. The activity of the phosphoinositide phosphatase in Ci-VSP is tuned within a physiological range of membrane potential. Immunocytochemical studies show that Ci-VSP is expressed in Ciona sperm tail membranes, suggesting a role in sperm function or morphology. Our data demonstrate that voltage sensing can function beyond channel proteins and thus more ubiquitously than previously appreciated. Less

Anklyc-G是一种模块化蛋白，在哺乳动物神经元的Ranvier节点和起始节段中的电压门控钠通道（Nav通道）的聚集中起关键作用。然而，ankeiv-G对Nav通道电生理特性的直接影响仍然是难以捉摸的。在这项研究中，我们探讨了是否ankrex-G有一个作用，在修改门控特性的神经元Nav1.6通道，主要是本地化的节点Ranvier和初始段。单独转染人Nav1.6 cDNA的TsA 201细胞表现出显著的持续钠电流（Ina-p）。另一方面，Ina-p在与anklove-G共表达时几乎未检测到。另一种锚蛋白Ankyrin-B没有表现出这种作用。锚蛋白的两种同种型之间的嵌合体的表达表明，锚蛋白-G的膜结合结构域对于降低Nav1.6的Ina-p是至关重要的。这些结果表明，ankrex-G不仅通过聚集Nav通道调节神经元兴奋性， ...更多信息 通过直接修改它们的信道选通。膜电位的变化影响离子通道和转运蛋白，从而改变细胞内的化学条件。已经提出了与膜电位偶联的其它信号传导途径，但其潜在机制尚不清楚。我们已经从海鞘中鉴定出一种新的蛋白质，其具有与电压门控通道的S1-S4区段同源的跨膜电压感应结构域和与磷酸酶和张力同源物（PTEN）类似的胞质结构域。这种蛋白质，命名为Ci-VSP（含磷酸酶的电压传感器），显示通道样的“门控”电流，并直接将膜电位的变化转化为磷酸肌醇的周转。Ci-VSP中磷酸肌醇磷酸酶的活性在膜电位的生理范围内调节。免疫细胞化学研究表明，Ci-VSP表达在玻璃海鞘精子尾膜，表明在精子功能或形态的作用。我们的数据表明，电压传感可以超越通道蛋白的功能，因此比以前认识到的更普遍。少

项目成果

Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19-deficient mice.

• DOI: 10.1083/jcb.200501154
• 发表时间: 2005-05-09
• 期刊: The Journal of cell biology
• 作者: Miyamoto T;Morita K;Takemoto D;Takeuchi K;Kitano Y;Miyakawa T;Nakayama K;Okamura Y;Sasaki H;Miyachi Y;Furuse M;Tsukita S
• 通讯作者: Tsukita S

電位センサーの動作原理と電位感受性酵素VSP

电压传感器和电压敏感酶VSP的工作原理

• 发表时间: 2006
• 期刊: 標準生理学(イオンチャンルの発現制御機構) 25.3月号
• 作者: 津元国親;倉田康孝;古谷和春;倉智嘉久.;川上英良;Mimura K; Nagai Y; Inoue K; Matsumoto J; Suhara T; Nishijo H; Takada M; Minamimoto T;岡村康司
• 通讯作者: 岡村康司

Regulation of Nay channels in sensory neurons

感觉神经元 Nay 通道的调节

• 发表时间: 2005
• 期刊: Trends in Pharmacological Sciences 10
• 作者: Chahine M^*;Ziane R;Vijayaragavan K;Okamura Y.
• 通讯作者: Okamura Y.

「神経系におけるイオンチャネル発現制御機構」ブレインサイエンスレビュー2005

“神经系统中的离子通道表达控制机制”《脑科学评论》2005

• 发表时间: 2005
• 作者: Kuroda K;Ito M;Shikano T;Awaji T;Yoda A;Takeuchi H;Kinoshita K;Miyazaki S;岡村康司;岡村 康司
• 通讯作者: 岡村 康司

Development of transient outward currents coupled with Ca^<2+>-induced Ca^<2+> release mediates oscillatory membrane potential in ascidi

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• 发表时间: 2004
• 期刊: J.Neurophysiol. 92
• 作者: K.Nakajo K;Y.OKAMRA
• 通讯作者: Y.OKAMRA