Ion Permeability of a Microtubule in Neuron Environment

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 Ca²⁺ 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 Ca²⁺, Na⁺, and K⁺. As a result, when the concentration of Ca²⁺ 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.