• behavior;
  • endothelin;
  • gene-engineered mice;
  • Schwann cells


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 (inline image ) mice. Histological analyses showed a decrease in the number of regenerated myelinated axons in inline image sciatic nerves. The delay in the recovery in inline image 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 inline image 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.