Shen Chun, Guo Wanlin
State Key Laboratory of Mechanics and Control of Mechanical Structure and Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education, and Institute of Nanoscience , Nanjing University of Aeronautics and Astronautics , Nanjing 210016 , China.
J Phys Chem Lett. 2018 Apr 19;9(8):2009-2014. doi: 10.1021/acs.jpclett.8b00324. Epub 2018 Apr 9.
Microtubules, constituted by end-to-end negatively charged α- and β-tubulin dimers, are long, hollow, pseudohelical cylinders with internal and external diameters of about 16 and 26 nm, respectively, and widely exist in cell cytoplasm, neuron axons, and dendrites. Although their structural functions in physiological processes, such as cell mitosis, cell motility, and motor protein transport, have been widely accepted, their role in neuron activity remains attractively elusive. Here we show a new function of microtubules: they can generate instant response to a calcium pulse because of their specific permeability for ions. Our comprehensive simulations from all-atom molecular dynamics to potential of mean force and continuum modeling reveal that K and Na ions can permeate through the nanopores in the microtubule wall easily, while Ca ions are blocked by the wall with a much higher free energy barrier. These cations are adsorbed to the surfaces of the wall with affinity decreasing in the sequence Ca, Na, and K. As a result, when the concentration of Ca ions increases outside the microtubule during neuronal excitation, K and Na ions will be driven into the microtubule, triggering subsequent axial ion redistribution within the microtubule. The results shed light on the possibility of the ion-permeable microtubules being involved in neural signal processing.
微管由首尾相连的带负电荷的α-和β-微管蛋白二聚体构成，是长的、中空的、假螺旋圆柱体，其内径和外径分别约为16纳米和26纳米，广泛存在于细胞质、神经元轴突和树突中。尽管它们在诸如细胞有丝分裂、细胞运动和运动蛋白运输等生理过程中的结构功能已被广泛认可，但其在神经元活动中的作用仍然极具吸引力且难以捉摸。在此，我们展示了微管的一项新功能：由于其对离子的特定通透性，它们能够对钙脉冲产生即时反应。我们从全原子分子动力学到平均力势和连续介质建模的综合模拟表明，钾离子和钠离子能够轻松穿过微管壁上的纳米孔，而钙离子则被管壁以高得多的自由能势垒阻挡。这些阳离子以亲和力按钙、钠、钾的顺序递减的方式吸附在管壁表面。因此，当神经元兴奋时微管外部的钙离子浓度增加，钾离子和钠离子将被驱动进入微管，引发微管内随后的轴向离子重新分布。这些结果揭示了离子可通透的微管参与神经信号处理的可能性。
