Energy Metabolism in Mouse Sciatic Nerve A Fibres during Increased Energy Demand

Rich, Laura R.; Ransom, Bruce R.; Brown, Angus M.

Abstract

The ability of sciatic nerve A fibres to conduct action potentials relies on an adequate supply of energy substrate, usually glucose, to maintain necessary ion gradients. Under our ex vivo experimental conditions, the absence of exogenously applied glucose triggers Schwann cell glycogen metabolism to lactate, which is transported to axons to fuel metabolism, with loss of the compound action potential (CAP) signalling glycogen exhaustion. The CAP failure is accelerated if tissue energy demand is increased by high‐frequency stimulation (HFS) or by blocking lactate uptake into axons using cinnemate (CIN). Imposing HFS caused CAP failure in nerves perfused with 10 mM glucose, but increasing glucose to 30 mM fully supported the CAP and promoted glycogen storage. A combination of glucose and lactate supported the CAP more fully than either substrate alone, indicating the nerve is capable of simultaneously metabolising each substrate. CAP loss re-sulting from exposure to glucose‐free artificial cerebrospinal fluid (aCSF) could be fully reversed in the absence of glycogen by addition of glucose or lactate when minimally stimulated, but imposing HFS resulted in only partial CAP recovery. The delayed onset of CAP recovery coincided with the release of lactate by Schwann cells, suggesting that functional Schwann cells are a prerequisite for CAP recovery.

Citation

Rich, L. R., Ransom, B. R., & Brown, A. M. (2022). Energy Metabolism in Mouse Sciatic Nerve A Fibres during Increased Energy Demand. Metabolites, 12(6), Article 505. https://doi.org/10.3390/metabo12060505

• Journal Article Type: Article
• Acceptance Date: May 30, 2022
• Online Publication Date: May 31, 2022
• Publication Date: Jun 1, 2022
• Deposit Date: Jun 22, 2022
• Publicly Available Date: Jun 22, 2022
• Journal: Metabolites
• Electronic ISSN: 2218-1989
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 6
• Article Number: 505
• DOI: https://doi.org/10.3390/metabo12060505
• Keywords: Molecular Biology; Biochemistry; Endocrinology, Diabetes and Metabolism
• Public URL: https://nottingham-repository.worktribe.com/output/8309934
• Publisher URL: https://www.mdpi.com/2218-1989/12/6/505