Action potentials (spikes) are regenerated at each node of Ranvier during saltatory transmission along a myelinated axon. The high density of voltage-gated sodium channels required by nodes to reliably transmit spikes increases the risk of ectopic spike generation in the axon. Here we show that ectopic spiking is avoided because KV1 channels prevent nodes from responding to slow depolarization; instead, axons respond selectively to rapid depolarization because KV1 channels implement a high-pass filter. To characterize this filter, we compared spike initiation properties in the soma and axon of CA1 pyramidal neurons from mice of both sexes, using spatially restricted photoactivation of channelrhodopsin-2 (ChR2) to evoke spikes in either region while simultaneously recording at the soma. Somatic photostimulation evoked repetitive spiking whereas axonal photostimulation evoked transient spiking. Blocking KV1channels converted the axon photostimulation response to repetitive spiking and encouraged spontaneous ectopic spike initiation in the axon. According to computational modeling, the high-pass filter implemented by KV1 channels matches the axial current waveform associated with saltatory conduction, enabling axons to faithfully transmit digital signals by maximizing their signal-to-noise ratio for this task. Specifically, a node generates a single spike only when rapidly depolarized, which is precisely what occurs during saltatory conduction when a pulse of axial current(triggered by a spike occurring at the upstream node) reaches the next node. The soma and axon use distinct spike initiation mechanisms (filters) appropriate for the task required of each region, namely, analog-to-digital transduction in the soma versus digital signal transmission in the axon.
Model Type: Axon
Region(s) or Organism(s): Hippocampus
Cell Type(s): Myelinated neuron
Currents: Channelrhodopsin (ChR); I K; I K,leak; I Na, slow inactivation; I_K,Na
Receptors:
Genes:
Transmitters:
Model Concept(s):
Simulation Environment:
Implementer(s): Abdollahi, Nooshin [nooshin.abdollahi at mail.utoronto.ca]
References:
Abdollahi N, Xie YF, Ratté S, Prescott SA. (2025). KV1 channels enable myelinated axons to transmit spikes reliably without spiking ectopically. The Journal of neuroscience : the official journal of the Society for Neuroscience. [PubMed]