The Nax channel: What it is and what it does

Masaharu Noda, Takeshi Y. Hiyama

Research output: Contribution to journalReview article

18 Citations (Scopus)

Abstract

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
JournalNeuroscientist
Volume21
Issue number4
DOIs
Publication statusPublished - Aug 21 2015
Externally publishedYes

Fingerprint

Hypernatremia
Body Fluids
Autoimmunity
Subfornical Organ
Endothelin-3
Ganglioneuroma
Endothelin B Receptors
Voltage-Gated Sodium Channels
Sodium Channels
Intravenous Immunoglobulins
Schwann Cells
Knockout Mice
Intravenous Injections
Neuroglia
Protein Kinase C
Mammals
Anti-Idiotypic Antibodies
Homeostasis
Salts
Sodium

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

The Nax channel : What it is and what it does. / Noda, Masaharu; Hiyama, Takeshi Y.

In: Neuroscientist, Vol. 21, No. 4, 21.08.2015, p. 399-412.

Research output: Contribution to journalReview article

Noda, Masaharu ; Hiyama, Takeshi Y. / The Nax channel : What it is and what it does. In: Neuroscientist. 2015 ; Vol. 21, No. 4. pp. 399-412.
@article{134111d69fdd42f497bf2cb2fc1a7876,
title = "The Nax channel: What it is and what it does",
abstract = "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.",
keywords = "autoimmune channelopathy, body-fluid homeostasis, endothelin, essential hypernatremia, Na-level sensor, Na channel, paraneoplastic neurologic disorder",
author = "Masaharu Noda and Hiyama, {Takeshi Y.}",
year = "2015",
month = "8",
day = "21",
doi = "10.1177/1073858414541009",
language = "English",
volume = "21",
pages = "399--412",
journal = "Neuroscientist",
issn = "1073-8584",
publisher = "SAGE Publications Inc.",
number = "4",

}

TY - JOUR

T1 - The Nax channel

T2 - What it is and what it does

AU - Noda, Masaharu

AU - Hiyama, Takeshi Y.

PY - 2015/8/21

Y1 - 2015/8/21

N2 - 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.

AB - 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.

KW - autoimmune channelopathy

KW - body-fluid homeostasis

KW - endothelin

KW - essential hypernatremia

KW - Na-level sensor

KW - Na channel

KW - paraneoplastic neurologic disorder

UR - http://www.scopus.com/inward/record.url?scp=84937576271&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937576271&partnerID=8YFLogxK

U2 - 10.1177/1073858414541009

DO - 10.1177/1073858414541009

M3 - Review article

C2 - 24962095

AN - SCOPUS:84937576271

VL - 21

SP - 399

EP - 412

JO - Neuroscientist

JF - Neuroscientist

SN - 1073-8584

IS - 4

ER -