Centre for Neuroscience, Surgery and Trauma, Blizard Institute, QMUL, 4 Newark Street Whitechapel, London, E1 2AT, UK.
Sci Rep. 2020 Jul 29;10(1):12755. doi: 10.1038/s41598-020-69728-y.
In multiple sclerosis, exacerbation of symptoms with rising body temperature is associated with impulse conduction failure. The mechanism is not fully understood. Remarkably, normal optic nerve axons also show temperature dependent effects, with a fall in excitability with warming. Here we show two properties of optic nerve axons, accommodation and inward rectification (I), respond to temperature changes in a manner consistent with a temperature dependent membrane potential. As we could find no evidence for the functional expression of K7.2 in the axons, using the K channel blocker tetraethylammonium ions, we suggest this may explain the membrane potential lability. In order to understand how the axonal membrane potential may show temperature dependence, we have developed a hypothesis involving the electroneutral movement of Na ions across the axon membrane, that increases with increasing temperature with an appropriate Q. Part, but probably not all, of the electroneutral Na movement is eliminated by removing extracellular Cl or exposure to bumetanide, consistent with the involvement of the transporter NKCC1. Numerical simulation suggests a change in membrane potential of - 15-20 mV mimics altering temperature between room and physiological in the largest axons.
在多发性硬化症中，症状的加剧与体温升高有关，这与冲动传导失败有关。其机制尚未完全阐明。值得注意的是，正常的视神经轴突也表现出温度依赖性效应，随着温度升高，兴奋性下降。在这里，我们展示了视神经轴突的两个特性，适应和内向整流（I），其对温度变化的响应方式与依赖于温度的膜电位一致。由于我们在轴突中没有发现 K7.2 功能表达的证据，因此我们使用钾通道阻断剂四乙铵离子，我们认为这可以解释膜电位的不稳定性。为了了解轴突膜电位如何表现出温度依赖性，我们提出了一个假设，涉及到 Na 离子在轴突膜中的电中性运动，该运动随温度升高而增加，与适当的 Q 值有关。部分但不是全部的电中性 Na 运动可以通过去除细胞外 Cl 或暴露于布美他尼来消除，这与转运蛋白 NKCC1 的参与一致。数值模拟表明，膜电位的变化为 -15-20 mV 可以模拟在最大的轴突中改变室温与生理温度之间的差异。
