[论文解读] Nerves and anaesthesia: A physics perspective on medicine

Thomas Heimburg|arXiv (Cornell University)|Sep 8, 2014

Lipid Membrane Structure and Behavior参考文献 30被引用 3

一句话总结

该论文提出了一种基于物理的理论，通过膜相变解释神经冲动传导和麻醉机制，其中神经脉冲被建模为熔融脂质膜中的孤立子。该理论表明，麻醉剂会降低膜的熔点，从而抑制兴奋性，并通过脂质溶解度和相变行为解释了梅耶-奥弗顿相关性。

ABSTRACT

We present a recent theory for nerve pulse propagation and anesthesia and argue that both nerve activity and the action of anesthetics can be understood on the basis of simple physical laws. It was found experimentally that biological membranes melt from a solid state to a liquid state just below physiological temperature. Such melting processes have a profound influence on the physical properties of cell membranes. They make it possible for mechanical pulses (solitons) to travel along nerve axons. In these pulses, a region of solid phase travels in the liquid nerve membrane. These pulses display many properties associated with the action potential in nerves. Both general and local anesthetics lower melting temperatures of membranes. Thus, they make it more difficult to excite the nerve membrane. Since hydrostatic pressure increases melting temperatures, it counteracts anesthesia. This theory has the virtue of providing a simple explanation of the famous Meyer-Overton correlation, which states that the effectiveness of an anesthetic is proportional to its solubility in the lipid membranes of cells. We offer evidence that this concept if also applicable to local anesthesia. Finally, we show that the presence of transitions has an influence on channel activity that can arise even in the absence of proteins. The miracle of the appropriateness of the language of mathematics for the formula- tion of the laws of physics is a wonderful gift which we neither understand nor de- serve. We should be grateful for it and hope that it will remain valid in future re- search (Eugene Wigner, 1960).

研究动机与目标

• 使用凝聚态物理和膜相变原理解释神经冲动传导。
• 通过将麻醉剂效力与脂质膜溶解度和熔融行为相关联，解决长期存在的梅耶-奥弗顿相关性问题。
• 研究麻醉剂和静水压力如何调节膜相态和神经兴奋性。
• 探讨离子通道活性是否可仅由物理膜性质产生，而无需依赖蛋白质结构。

提出的方法

• 将神经膜建模为在生理温度附近在固相与液相之间转变的双相系统。
• 应用孤立子理论描述作为膜中局部相边界传播的机械脉冲。
• 运用热力学原理，将麻醉剂在脂质中的溶解度与膜熔点变化相关联。
• 分析静水压力对膜相变的影响及其与麻醉作用的拮抗关系。
• 基于相变热力学推导麻醉剂效力与脂质溶解度之间的关系。
• 证明即使在缺乏膜蛋白的情况下，脂质膜的相变也能影响离子运输。

实验结果

研究问题

• RQ1 如何通过脂质膜中的物理相变解释神经冲动传导？
• RQ2 为何麻醉剂效力与脂质溶解度相关，如梅耶-奥弗顿规则所述？
• RQ3 静水压力在逆转麻醉效应中起什么作用，其与膜熔点的关系如何？
• RQ4 在未嵌入蛋白质的情况下，是否可由物理膜性质产生类似离子通道的活性？
• RQ5 膜中类似孤立子的脉冲如何再现动作电位的关键特征？

主要发现

• 神经冲动传导被解释为在接近生理温度下经历固-液相变的脂质膜中沿相边界传播的类似孤立子的机械脉冲。
• 全身性和局部麻醉剂降低神经膜的熔点，减少相变可能性，从而抑制神经兴奋性。
• 静水压力提高膜的熔点，抵消麻醉剂的作用，与实验观察一致。
• 该理论为梅耶-奥弗顿相关性提供了物理解释，表明麻醉剂效力与脂质溶解度成正比，这是由于其对膜相行为的影响。
• 即使在缺乏蛋白质通道的情况下，脂质膜的相变也能影响离子运输和膜电位，表明某些电生理现象可能具有物理起源。
• 该模型通过热力学驱动系统中相边界动力学，再现了动作电位的关键生物物理特征。