Concentration-sensitive sodium channel Nax

浓度敏感钠通道 Nax

基本信息

批准号：
14580781
负责人：
WATANABE Eiji
金额：
$ 2.3万
依托单位：
Okazaki National Research Institutes
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580781/
关键词：
sodium salt sensor knockout channel circumventricular neuron hypertension ノックアウトマウス脳室

项目摘要

Cultured cells derived from the circumventricular organs were subjected to ion-imaging sutdies. When extracellular sodiun concentration was increased to 150 mM〜170mM, an increase of intracellular sodium concentration was observed. This response was not observed in cells derived from the Nax-deficient mice. These results suggest that Nax is a sodium channel sensitive to extracellular sodium increase. Next, stable cell lines expressing Nax were established. The response was also observed in these cells, but not in non-Nax-expressing cells. Thus, it is clear that Nax is a novel type of sodium channel activated in response to extracellular sodium level.Sodium sensing mechanism of the brain was studied using by the Nax-knockout mice. Under dehydrate conditions, animals avoid hypertonic sodium solution, whereas the Nax-knockout mice keep drinking it under such conditions. Infusion of hypertonic sodium sokution to the cerebral ventricle of mice caused aversive behavior for salt-intake in wild-type mice. On the other hand, such aversive behavior was not observed in the knockout mice. Next, Nax cDNA was introduced to the brain of the knockout mice with Adenoviral expression vector. The introduction of Nax cDNA to the subfornical organ conferred the salt-avoiding behavior under dehydrated conditions on the knockout mice. These results demonstrate that the subfornical organ is the center of the sodium sensing mechanism and that Nax is indispensable for the sodium-sensing mechanism in the brain.

对源自心室周围器官的培养细胞进行离子成像研究，当细胞外钠浓度增加至150mM〜170mM时，观察到细胞内钠浓度增加，而在源自Nax缺陷小鼠的细胞中未观察到这种反应。这些结果表明Nax是对细胞外钠增加敏感的钠通道，随后建立了表达Nax的稳定细胞系，但在这些细胞中也观察到了这种反应。因此，很明显，Nax 是一种响应细胞外钠水平而激活的新型钠通道。通过 Nax 敲除小鼠在脱水条件下研究了大脑的钠感应机制。避免高渗钠溶液，而Nax敲除小鼠在这种情况下继续饮用高渗钠溶液会导致野生型小鼠出现厌恶盐摄入的行为。另一方面，在敲除小鼠中没有观察到这种厌恶行为。接下来，用腺病毒表达载体将Nax cDNA引入敲除小鼠的大脑中，将Nax cDNA引入穹窿下器官，赋予了脱水条件下的避盐行为。这些结果表明穹窿下器官是钠感应机制的中心，Nax 对于大脑中的钠感应机制是不可或缺的。