Channel properties of Nax expressed in neurons

PLoS One. 2015 May 11;10(5):e0126109. doi: 10.1371/journal.pone.0126109. eCollection 2015.

Abstract

Nax is a sodium-concentration ([Na+])-sensitive Na channel with a gating threshold of ~150 mM for extracellular [Na+] ([Na+]o) in vitro. We previously reported that Nax was preferentially expressed in the glial cells of sensory circumventricular organs including the subfornical organ, and was involved in [Na+] sensing for the control of salt-intake behavior. Although Nax was also suggested to be expressed in the neurons of some brain regions including the amygdala and cerebral cortex, the channel properties of Nax have not yet been adequately characterized in neurons. We herein verified that Nax was expressed in neurons in the lateral amygdala of mice using an antibody that was newly generated against mouse Nax. To investigate the channel properties of Nax expressed in neurons, we established an inducible cell line of Nax using the mouse neuroblastoma cell line, Neuro-2a, which is endogenously devoid of the expression of Nax. Functional analyses of this cell line revealed that the [Na+]-sensitivity of Nax in neuronal cells was similar to that expressed in glial cells. The cation selectivity sequence of the Nax channel in cations was revealed to be Na+ ≈ Li+ > Rb+ > Cs+ for the first time. Furthermore, we demonstrated that Nax bound to postsynaptic density protein 95 (PSD95) through its PSD95/Disc-large/ZO-1 (PDZ)-binding motif at the C-terminus in neurons. The interaction between Nax and PSD95 may be involved in promoting the surface expression of Nax channels because the depletion of endogenous PSD95 resulted in a decrease in Nax at the plasma membrane. These results indicated, for the first time, that Nax functions as a [Na+]-sensitive Na channel in neurons as well as in glial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / cytology
  • Animals
  • Cell Line
  • Cells, Cultured
  • Immunohistochemistry
  • Mice
  • Neurons / metabolism*
  • Rats
  • Sodium / metabolism
  • Voltage-Gated Sodium Channels / metabolism*

Substances

  • Voltage-Gated Sodium Channels
  • Sodium

Grants and funding

This work was supported by MEXT/JSPS KAKENHI (Grant Numbers; 25830021 to MM; 26293043 to TYH; and 24220010 to MN) and the Okazaki ORION project. URL: http://www.jsps.go.jp/english/e-grants/grants01.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.