Involvement of Nax sodium channel in peripheral nerve regeneration via lactate signaling

Sawako Unezaki, Tayo Katano, Takeshi Y. Hiyama, Nguyen H. Tu, Satoru Yoshii, Masaharu Noda, Seiji Ito

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Nax, a sodium concentration-sensitive sodium channel, is expressed in non-myelinating Schwann cells of the adult peripheral nervous system, but the pathophysiological role remains unclear. We found that functional recovery of the hind paw responses from the sciatic nerve transection was delayed in Nax knockout (Nax-/- ) mice. Histological analyses showed a decrease in the number of regenerated myelinated axons in Nax-/- sciatic nerves. The delay in the recovery in Nax-/- mice was improved by lactate and inhibited by a monocarboxylate transporter inhibitor. In vitro experiments using cultured Schwann cells showed that lactate release was enhanced by endothelin (ET)-1 and blocked by an ET receptor type B antagonist. Here, it is conceivable that Nax was activated by ET-1. The amount of lactate release by ET-1 was lower in Nax-/- mice than in wild-type mice. These results indicated that Nax is functionally coupled to ET for lactate release via ET receptor type B and is involved in peripheral nerve regeneration. Nax, a sodium concentration-sensitive sodium channel, is expressed in non-myelinating Schwann cells of adult peripheral nervous system. We found that functional recovery of the hind paw responses from the sciatic nerve transection was delayed in Nax-knockout (Nax-/-) mice. The present study demonstrates that Nax is functionally coupled to endothelin for lactate release via endothelin receptor type B and involved in peripheral nerve regeneration.

Original languageEnglish
Pages (from-to)720-729
Number of pages10
JournalEuropean Journal of Neuroscience
Volume39
Issue number5
DOIs
Publication statusPublished - Mar 1 2014
Externally publishedYes

Fingerprint

Nerve Regeneration
Sodium Channels
Peripheral Nerves
Lactic Acid
Knockout Mice
Schwann Cells
Endothelin-1
Sciatic Nerve
Endothelin B Receptors
Endothelins
Peripheral Nervous System
Sodium
Axons
Cultured Cells

Keywords

  • Behavior
  • Endothelin
  • Gene-engineered mice
  • Schwann cells

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Involvement of Nax sodium channel in peripheral nerve regeneration via lactate signaling. / Unezaki, Sawako; Katano, Tayo; Hiyama, Takeshi Y.; Tu, Nguyen H.; Yoshii, Satoru; Noda, Masaharu; Ito, Seiji.

In: European Journal of Neuroscience, Vol. 39, No. 5, 01.03.2014, p. 720-729.

Research output: Contribution to journalArticle

Unezaki, Sawako ; Katano, Tayo ; Hiyama, Takeshi Y. ; Tu, Nguyen H. ; Yoshii, Satoru ; Noda, Masaharu ; Ito, Seiji. / Involvement of Nax sodium channel in peripheral nerve regeneration via lactate signaling. In: European Journal of Neuroscience. 2014 ; Vol. 39, No. 5. pp. 720-729.
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