A possible mechanism of repetitive firing of myelinated axon

Abstract

A unique mechanism is proposed according to which processes within the internodal axolemma are responsible for repetitive activation of myelinated axon with deficit of internodal potassium conductance. A numerical simulation of activity in axon with 21 nodes was performed. The axon was represented by cables for axoplasmic and periaxonal spaces. Accumulation and diffusion of ions were taken into account. Fine segmentation of each internode (338 segments) allowed simulation of internodal activation in response to a normal saltatorial action potential initiated by a short stimulus. The internodal membrane without potassium conductance experienced considerable depolarization. This resulted in formation of a transition zone and significant currents that caused repetitive activation of the internode and neighbor node. Decline of periaxonal sodium concentration during the spike production or lowering of sodium channel density decreased the sodium currents. As a result, the interspike intervals increased up to cessation of the burst. The cessation was reversible.

A possible link of oxaliplatin‐induced neuropathy with potassium channel deficit

“…8) differed from those in proximity to the remote nodes. The small peaks in The increase is similar to the case considered for generalized blockage of potassium channels in all internodes, 27 where it was related to the reduction in concentration of periaxonal sodium ions with time.…”

“…In any case, after the passing of a saltatory action potential (sAP), and of the internodal action potentials induced by it, 26 transition zones were formed at the boundaries of the internodal region devoid of potassium channels. 27 In turn, these zones became sources of internodal action potentials that back-propagated to the closest nodes. If the nodes were activated by these internodal waves, an after-discharge was produced that propagated saltatorially from node to node in opposite directions from the region devoid of potassium channels.…”

“…[28][29][30][31][32] Ionic accumulation in periaxonal and intracellular spaces was taken into account. 26,27 The simulations were initiated by intracellular stimulation of the first node of Ranvier by a single rectangular current pulse with an intensity of 14 nA and duration 50 ls applied at time zero. Channel gating (G) for sodium (na) as well as for fast (kf) and slow (ks) potassium ions is summarized as follows 33 :…”

“…Nerve hyperexcitability in patients treated with oxaliplatin has been shown to be similar to the clinical manifestations of neuromyotonia. 12,14 However, in the study by Dimitrov,27 the potassium channels were blocked in all internodes of myelinated fibers. This hardly occurs immediately after oxaliplatin infusion.…”

“…Dimitrov 26 proposed a model predicting that the very thin periaxonal space (about a few nanometers) made the low density of internodal sodium channels sufficient for generation of active internodal processes. Based on this model, a mechanism of MA hyperactivity, 27 induced by blockage of internodal potassium channels, was proposed. The mechanism was related to processes in patients with neuromyotonia who frequently have antibodies to fast potassium channels.…”