[论文解读] Initiation and blocking of the action potential in the axon in a weak ultrasonic field

Mikhail N. Shneider, Mikhail Pekker|arXiv (Cornell University)|Sep 23, 2013

Photoreceptor and optogenetics research参考文献 23被引用 1

一句话总结

本研究证明，微弱的超声场可重新分布轴突起始段的电压门控钠通道，降低动作电位阈值并实现自发放电，而过度重新分布则会阻断信号传导。利用霍奇金-赫克斯利模型，研究显示超声产生的非热电声力可在远低于空化或加热效应发生强度下诱导这些变化，表明超声神经调控和非侵入性麻醉具有潜在应用前景。

ABSTRACT

Abstract In this paper we analyzed the effect of ultrasound on the redistribution of the transmembrane ion channels in the initial segment of the myelinated axon of a neuron. It is shown on the basis of Hodgkin-Huxley model of axon, that redistribution of the density of transmembrane sodium channels may reduce the threshold of the action potential, up to its spontaneous initiation. At significant redistribution of sodium channels in membrane, the zones of rarefaction of thetransmembrane channels density are formed blocking the propagation of the action potential. It is shown that the intensity of ultrasound at which the effect of transmembrane channels redistribution becomes noticeable is significantly greater than the intensity at which cavitation and overheating due to the ultrasound absorption occurs. However, as shown on an example of squid axon, the forced resonant electroacoustic oscillations excited in the membrane by the longitudinal electric component of the microwave may result in the transmembrane channels redistribution without essential heating. The intensity of the microwave, which may cause a spontaneous excitation of the action potential or its blocking on many orders of magnitude lower than the intensity at which come into play the thermal effects. The blocking effect of the action potential can be used in anesthesia.

研究动机与目标

• 研究微弱超声场如何影响轴突起始段离子通道分布。
• 确定超声是否可在无热效应的情况下引发或阻断动作电位。
• 探讨利用超声实现非侵入性神经调控和麻醉的可行性。
• 分析超声纵向电场分量在诱导神经膜电声振荡中的作用。

提出的方法

• 采用轴突的霍奇林-赫克斯利模型，模拟超声暴露下膜电位离子通道动力学的变化。
• 该模型分析了由超声机械力引起的轴突起始段钠通道密度的重新分布。
• 研究评估了在不同钠通道密度下动作电位起始的阈值。
• 评估了诱导通道重新分布的超声强度阈值与导致空化或加热等热效应的阈值。
• 对膜内强制共振电声振荡进行建模，以解释非热性通道重新分布机制。
• 使用乌贼巨轴突作为模型系统，估算可观测效应的现实强度水平。

实验结果

研究问题

• RQ1 微弱超声场是否可诱导轴突起始段电压门控钠通道的重新分布？
• RQ2 与热效应相比，超声强度达到何种水平时通道重新分布才变得显著？
• RQ3 超声诱导的通道重新分布是否可导致动作电位的自发起始？
• RQ4 过度的通道重新分布是否会阻断动作电位的传导？
• RQ5 能否利用超声产生的非热电声力实现神经调控或麻醉？

主要发现

• 轴突起始段钠通道的重新分布可降低动作电位起始阈值，导致自发放电。
• 过度重新分布会形成钠通道密度低的区域，从而阻断动作电位传导。
• 诱导通道重新分布所需的超声强度远低于空化或热损伤的阈值。
• 膜内强制电声振荡可在无显著加热的情况下重新分布通道，实现非热性神经调控。
• 诱导动作电位起始或阻断的阈值强度比热效应阈值低多个数量级。
• 通过通道重新分布阻断动作电位的效应表明，其在基于超声的非侵入性麻醉中具有潜在应用价值。