Concentration-sensitive sodium channel Nax

来自心室周围器官的培养细胞进行离子成像研究。当胞外钠浓度增加到150mm ~ 170mM时，胞内钠浓度增加。这种反应在来自na -缺陷小鼠的细胞中没有观察到。这些结果表明Nax是一个对细胞外钠增加敏感的钠通道。然后，建立表达Nax的稳定细胞系。在这些细胞中也观察到这种反应，但在非表达nax的细胞中没有。因此，很明显，钠离子通道是一种响应细胞外钠水平而激活的新型钠通道。通过敲除钠基因小鼠，研究了脑内钠敏感机制。在脱水条件下，动物避免高渗钠溶液，而在这种情况下，敲除nax的小鼠继续饮用高渗钠溶液。小鼠脑室输注高渗钠溶液引起野生型小鼠对盐摄入的厌恶行为。另一方面，在基因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导入敲除小鼠的大脑。将Nax cDNA引入皮层下器官，使敲除小鼠在脱水条件下具有避盐行为。这些结果表明，皮层下器官是钠敏感机制的中心，而钠在大脑钠敏感机制中是不可或缺的。

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.