Faisal A Aldo, White John A, Laughlin Simon B
Department of Zoology, University of Cambridge, Downing Street, CB2 3EJ Cambridge, United Kingdom.
Curr Biol. 2005 Jun 21;15(12):1143-9. doi: 10.1016/j.cub.2005.05.056.
The action potential (AP) is transmitted by the concerted action of voltage-gated ion channels. Thermodynamic fluctuations in channel proteins produce probabilistic gating behavior, causing channel noise. Miniaturizing signaling systems increases susceptibility to noise, and with many cortical, cerebellar, and peripheral axons <0.5 mum diameter [1, 2 and 3], channel noise could be significant [4 and 5]. Using biophysical theory and stochastic simulations, we investigated channel-noise limits in unmyelinated axons. Axons of diameter below 0.1 microm become inoperable because single, spontaneously opening Na channels generate spontaneous AP at rates that disrupt communication. This limiting diameter is relatively insensitive to variations in biophysical parameters (e.g., channel properties and density, membrane conductance and leak) and will apply to most spiking axons. We demonstrate that the essential molecular machinery can, in theory, fit into 0.06 microm diameter axons. However, a comprehensive survey of anatomical data shows a lower limit for AP-conducting axons of 0.08-0.1 microm diameter. Thus, molecular fluctuations constrain the wiring density of brains. Fluctuations have implications for epilepsy and neuropathic pain because changes in channel kinetics or axonal properties can change the rate at which channel noise generates spontaneous activity.
动作电位（AP）通过电压门控离子通道的协同作用进行传递。通道蛋白中的热力学波动会产生概率性门控行为，从而导致通道噪声。信号系统的小型化会增加对噪声的敏感性，并且许多皮质、小脑和外周轴突的直径小于0.5微米[1,2和3]，通道噪声可能会很显著[4和5]。我们运用生物物理理论和随机模拟，研究了无髓鞘轴突中的通道噪声极限。直径小于0.1微米的轴突无法正常工作，因为单个自发开放的钠通道会以破坏通信的速率产生自发动作电位。这个极限直径对生物物理参数（例如通道特性和密度、膜电导和漏电）的变化相对不敏感，并且适用于大多数产生动作电位的轴突。我们证明，理论上基本的分子机制可以装入直径为0.06微米的轴突中。然而，对解剖学数据的全面调查显示，传导动作电位的轴突的下限直径为0.08 - 0.1微米。因此，分子波动限制了大脑的布线密度。波动对癫痫和神经性疼痛有影响，因为通道动力学或轴突特性的变化会改变通道噪声产生自发活动的速率。
