Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance

Abstract

The myelinated nerve fibre is formed by an axon and Schwann cells or oligodendrocytes that sheath the axon by winding around it in tight myelin layers. Repetitive stimulation of a fibre is known to result in accumulation of extracellular potassium ions, especially between the axon and the myelin. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from no block (less than 100 Hz) to a complete block (greater than 500 Hz). The transitional patterns include intermittent periodic block with interleaved spiking and non-spiking intervals of different relative duration as well as an unstable regime with chaotic switching between the spiking and non-spiking states. Intermittent conduction blocks are accompanied by oscillations of extracellular potassium. The mechanism of conductance block based on myelin restructuring complements the already known and modelled block via hyperpolarization mediated by the axonal sodium pump and potassium depolarization.

Myelinated axon physiology and regulation of neural circuit function

“…As noted above voltage‐gated K + channels are localized to the axonal juxtaparanode and are thought to mediate the vast majority of AP driven K + efflux into the confined periaxonal space (Wang et al, ; reviewed in Salzer, ; Rash, ) (Figure ). Indeed, in silico assessments predict that elevation of periaxonal K + driven by high frequency neuronal activity could lead to various excitability states of the axon (Bellinger, Miyazawa, & Steinmetz, ; Bostock, Baker, & Reid, ; Brazhe, Maksimov, Mosekilde, & Sosnovtseva, ). Moreover, local elevations of K + are likely to increase local excitability and the likelihood of excitotoxicity and, furthermore, osmotic swelling.…”

Comparative study to evaluate the effects of peritoneal and hemodialysis on peripheral nerve function

“…A possible explanation for the marked differences in nerve excitability between these groups may be related to the greater exposure of HD patients to marked fluctuations in serum K + . These fluctuations, rather than hyperkalemia per se , may have a detrimental effect on the paranodal region due to the role of myelin in maintaining K + homeostasis in the submyelinic space …”

“…These fluctuations, rather than hyperkalemia per se, may have a detrimental effect on the paranodal region due to the role of myelin in maintaining K 1 homeostasis in the submyelinic space. 30,31 Early dialysis studies suggested that PD may provide better removal of middle molecules and that this may confer a neurologic benefit. 32 However, modern high-flux HD membranes (such as those used in this study) have superior middle molecule clearances than PD, 33 and thus middle molecule clearance is unlikely to play a role in the differences reported here.…”

A model of electrical impedance tomography implemented in nerve-cuff for neural-prosthetics control

“…In myelinated fibres, the ion channels on the node of Ranvier control the majority of the transmembrane ion-flux during the depolarisation phase of an action potential. Membrane conductivity at the node of Ranvier was calculated using parameters and equations from (Brazhe, Maksimov et al 2011) as the sum of the fast Sodium, persistent Sodium, and slow Potassium ion channels, as well as the passive membrane leakage.…”