C-fiber recovery cycle supernormality depends on ion concentration and ion channel permeability

Biophysical Journal
Jenny TigerholmErik Fransén

Abstract

Following each action potential, C-fiber nociceptors undergo cyclical changes in excitability, including a period of superexcitability, before recovering their basal excitability state. The increase in superexcitability during this recovery cycle depends upon their immediate firing history of the axon, but also determines the instantaneous firing frequency that encodes pain intensity. To explore the mechanistic underpinnings of the recovery cycle phenomenon a biophysical model of a C-fiber has been developed. The model represents the spatial extent of the axon including its passive properties as well as ion channels and the Na/K-ATPase ion pump. Ionic concentrations were represented inside and outside the membrane. The model was able to replicate the typical transitions in excitability from subnormal to supernormal observed empirically following a conducted action potential. In the model, supernormality depended on the degree of conduction slowing which in turn depends upon the frequency of stimulation, in accordance with experimental findings. In particular, we show that activity-dependent conduction slowing is produced by the accumulation of intraaxonal sodium. We further show that the supernormal phase results from a reduced...Continue Reading

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Citations

Aug 5, 2017·Frontiers in Neurology·Barbara NamerMichiel Langeslag
Aug 14, 2020·Journal of Neurophysiology·Jenny TigerholmCarsten Dahl Mørch
Oct 22, 2020·Journal of Neurophysiology·Nicole A PelotWarren M Grill
Jun 27, 2021·The Journal of Physiology·Veronica BonalumeRichard Carr

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