Involvement of Nax sodium channel in peripheral nerve regeneration via lactate signaling |
| |
| Authors: | Sawako Unezaki Tayo Katano Takeshi Y. Hiyama Nguyen H. Tu Satoru Yoshii Masaharu Noda Seiji Ito |
| |
| Affiliation: | 1. Department of Medical Chemistry, Kansai Medical University, , Hirakata, 573‐1010 Japan;2. Division of Molecular Neurobiology, National Institute for Basic Biology, , Okazaki, 444‐8787 Japan;3. School of Life Science, The Graduate University for Advanced Studies, , Okazaki, 444‐8787 Japan;4. Department of Rehabilitation, Osaka Red Cross Hospital, , Osaka, 543‐8555 Japan |
| |
| 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 ( ) mice. Histological analyses showed a decrease in the number of regenerated myelinated axons in  sciatic nerves. The delay in the recovery in  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  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. |
| |
| Keywords: | behavior endothelin gene‐engineered mice Schwann cells |
|
|
