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Involvement of Na x sodium channel in peripheral nerve regeneration via lactate signaling
Author(s) -
Unezaki Sawako,
Katano Tayo,
Hiyama Takeshi Y.,
Tu Nguyen H.,
Yoshii Satoru,
Noda Masaharu,
Ito Seiji
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12436
Subject(s) - sciatic nerve , sodium channel , chemistry , peripheral nervous system , antagonist , sodium , receptor , endocrinology , medicine , in vitro , schwann cell , peripheral , central nervous system , biology , anatomy , biochemistry , organic chemistry
Abstract Na x , 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 Na x knockout ( N a x − / −) mice. Histological analyses showed a decrease in the number of regenerated myelinated axons in N a x − / −sciatic nerves. The delay in the recovery in N a x − / −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 Na x was activated by ET ‐1. The amount of lactate release by ET ‐1 was lower in N a x − / −mice than in wild‐type mice. These results indicated that Na x is functionally coupled to ET for lactate release via ET receptor type B and is involved in peripheral nerve regeneration.