Rich Laura R, Ransom Bruce R, Brown Angus M
School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
Department of Neurology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Metabolites. 2022 May 31;12(6):505. doi: 10.3390/metabo12060505.
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 resulting 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.
坐骨神经A纤维传导动作电位的能力依赖于充足的能量底物供应，通常是葡萄糖，以维持必要的离子梯度。在我们的离体实验条件下，缺乏外源性葡萄糖会触发雪旺细胞将糖原代谢为乳酸，乳酸被转运到轴突以促进代谢，复合动作电位（CAP）信号的丧失表明糖原耗竭。如果通过高频刺激（HFS）或使用肉桂酸盐（CIN）阻断乳酸向轴突的摄取来增加组织能量需求，CAP的衰竭会加速。施加HFS会导致灌注10 mM葡萄糖的神经出现CAP衰竭，但将葡萄糖浓度增加到30 mM可完全维持CAP并促进糖原储存。葡萄糖和乳酸的组合比单独使用任何一种底物更能充分维持CAP，这表明神经能够同时代谢每种底物。在最小刺激的情况下，当缺乏糖原时，通过添加葡萄糖或乳酸，暴露于无葡萄糖人工脑脊液（aCSF）导致的CAP丧失可完全逆转，但施加HFS仅导致CAP部分恢复。CAP恢复的延迟发生与雪旺细胞释放乳酸同时出现，这表明功能性雪旺细胞是CAP恢复的先决条件。
