Impaired sodium channels can enhance low-frequency signal conduction along myelinated axons

Sodium ion channels are crucial for the propagation of action potentials along myelinated axons. Any damage to these channels can significantly affect signal conduction. In this study, we systematically examined the impact of varying degrees of sodium channel dysfunction on axonal signal conduction. The propagation of action potentials in myelinated axons with sodium channel impairments was systematically investigated using a modified Hodgkin–Huxley model incorporating coupled left-shift (CLS) dynamics. By analyzing a single node of Ranvier (NoR) and a myelinated axon chain comprising 50 nodes, we identified distinct functional and dysfunctional signaling regions governed by the sodium channel impairment parameters ηAC (proportion of impaired channels) and VLS (left-shift voltage). The functional regions exhibited varying degrees of accelerated signal propagation due to enhanced depolarization kinetics. However, dysfunctional regions triggered spontaneous firing or propagation failure. The ability of axons to normally propagate signals within the functional region has subsequently been investigated. Quantitative analysis revealed that a gradual decline in signal fidelity is accompanied by a faster propagation time in functional regions. Information entropy calculations demonstrate significant signal degradation for high-frequency stimuli, attributed to refractory period constraints, whereas low-frequency stimuli maintained stable propagation. Our results indicate that axons with mild sodium channel impairment within an appropriate range can propagate signals effectively and faster than normal axons. Furthermore, mildly impaired sodium channels enable axons to transmit low-frequency signals more effectively, similar to their normal counterparts.