The Nax channel: What it is and what it does

Masaharu Noda, Takeshi Y. Hiyama

Research output: Contribution to journalReview articlepeer-review

30 Citations (Scopus)


Nax, which is preferentially expressed in the glial cells of sensory circumventricular organs in the brain, is a sodium channel that is poorly homologous to voltage-gated sodium channels. We previously reported that Nax is a sodium concentration ([Na+])-sensitive, but not a voltage-sensitive channel that is critically involved in body-fluid homeostasis. Nax-knockout mice do not stop ingesting salt even when dehydrated and transiently develop hypernatremia. [Na+] in body fluids is strictly controlled at 135 to 145 mM in mammals. Although the set point must be within this range, Nax was shown to have a threshold value of ∼150 mM for extracellular [Na+] ([Na+]o) for activation in vitro. Therefore, the [Na+]o dependency of Nax in vivo is presumably modified by an as yet unidentified mechanism. We recently demonstrated that the [Na+]o dependency of Nax in the subfornical organ was adjusted to the physiological range by endothelin-3. Pharmacological experiments revealed that endothelin receptor B signaling was involved in this modulation of Nax gating through protein kinase C and ERK1/2 activation. In addition, we identified a case of essential hypernatremia caused by autoimmunity to Nax. Occurrence of a ganglioneuroma composed of Schwann-like cells that robustly expressed Nax was likely to induce the autoimmune response in this patient. An intravenous injection of the immunoglobulin fraction of the patient's serum, which contained anti-Nax antibodies, into mice reproduced the patient's symptoms. This review provides an overview of the physiological functions of Nax by summarizing our recent studies.

Original languageEnglish
Pages (from-to)399-412
Number of pages14
Issue number4
Publication statusPublished - Aug 21 2015
Externally publishedYes


  • Na channel
  • Na-level sensor
  • autoimmune channelopathy
  • body-fluid homeostasis
  • endothelin
  • essential hypernatremia
  • paraneoplastic neurologic disorder

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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