期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：32
DOI：10.1073/pnas.2105795118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The reliability of spike propagation in axons is determined by complex interactions among ionic currents, ion pumps, and morphological properties. We use compartment-based modeling to reveal that interactions of diameter, myelination, and the Na/K pump determine the reliability of high-frequency spike propagation. By acting as a “reservoir” of nodal Na
+ influx, myelinated compartments efficiently increase propagation reliability. Although spike broadening was thought to oppose fast spiking, its effect on spike propagation is complicated, depending on the balance of Na
+ channel inactivation gate recovery, Na
+ influx, and axial charge. Our findings suggest that slow Na
+ removal influences axonal resilience to high-frequency spike propagation and that different strategies may be required to overcome this constraint in different neurons.
Axons reliably conduct action potentials between neurons and/or other targets. Axons have widely variable diameters and can be myelinated or unmyelinated. Although the effect of these factors on propagation speed is well studied, how they constrain axonal resilience to high-frequency spiking is incompletely understood. Maximal firing frequencies range from ∼1 Hz to >300 Hz across neurons, but the process by which Na/K pumps counteract Na
+ influx is slow, and the extent to which slow Na
+ removal is compatible with high-frequency spiking is unclear. Modeling the process of Na
+ removal shows that large-diameter axons are more resilient to high-frequency spikes than are small-diameter axons, because of their slow Na
+ accumulation. In myelinated axons, the myelinated compartments between nodes of Ranvier act as a “reservoir” to slow Na
+ accumulation and increase the reliability of axonal propagation. We now find that slowing the activation of K
+ current can increase the Na
+ influx rate, and the effect of minimizing the overlap between Na
+ and K
+ currents on spike propagation resilience depends on complex interactions among diameter, myelination, and the Na/K pump density. Our results suggest that, in neurons with different channel gating kinetic parameters, different strategies may be required to improve the reliability of axonal propagation.
关键词：encomputational model;action potential;node of Ranvier;electrogenic pumps;sodium dynamics
