The nanoscopic submyelin space mediates efficient K + uptake and shapes nodal action potentials

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Abstract

Myelin membranes are tightly connected to the axon, forming an electrical route for rapid saltatory conduction of action potentials from node to node. Beneath the myelin, adjacent to the node, lie voltage-gated potassium (K + ) channels, whose fundamental role in conduction remains poorly understood. Constrained by biological data, we developed a finite element model of a node of Ranvier encompassing an adaxonal membrane separating oligodendrocyte cytoplasm from the periaxonal space, and solved the full coupled set of physical equations governing electrodiffusion and voltage profiles at the nanoscale. Remarkably, we find that nodal action potentials invert at the inner adaxonal myelin membrane. The hyperpolarization-driven opening of myelinic Kir4.1 channels produces an instantaneous, powerful K + prebuffering, clamping the periaxonal K + concentration and enabling high-frequency action potential generation. Together, these findings indicate that the periaxon maintains an electrical feedback loop with the node, and suggest a key evolutionary advantage of juxtaparanodal K + channel positioning.

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