Concentration-sensitive sodium channel Nax

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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.