Abstract
The precise axonal distribution of specific potassium channels is known to secure the shape and frequency of action potentials in myelinated fibers. The low-threshold voltage-gated Kv1 channels located at the axon initial segment have a significant influence on spike initiation and waveform. Their role remains partially understood at the juxtaparanodes where they are trapped under the compact myelin bordering the nodes of Ranvier in physiological conditions. However, the exposure of Kv1 channels in de- or dys-myelinating neuropathy results in alteration of saltatory conduction. Moreover, cell adhesion molecules associated with the Kv1 complex, including Caspr2, Contactin2, and LGI1, are target antigens in autoimmune diseases associated with hyperexcitability such as encephalitis, neuromyotonia, or neuropathic pain. The clustering of Kv1.1/Kv1.2 channels at the axon initial segment and juxtaparanodes is based on interactions with cell adhesion molecules and cytoskeletal linkers. This review will focus on the trafficking and assembly of the axonal Kv1 complex in the peripheral and central nervous system (PNS and CNS), during development, and in health and disease.
Highlights
The precise distribution of K+ channels at the axon initial segment (AIS) and the nodes of Ranvier is critical to ensure the appropriate initiation and faithful propagation of action potentials (APs) along myelinated axons
We analyzed the trafficking and clustering of the Kv1 channels at the distinct axonal domains constituted by the AIS and juxtaparanodes
Specific molecular motors and adaptors are implicated in the anterograde axonal transport of Kv1 cargo and insertion at the cell membrane at specific sites
Summary
The precise distribution of K+ channels at the axon initial segment (AIS) and the nodes of Ranvier is critical to ensure the appropriate initiation and faithful propagation of action potentials (APs) along myelinated axons. A comprehensive view of the functional role of the diverse axonal K+ channels begins to emerge, taking into consideration the neuronal cell-type specificity In pathological conditions such as demyelinating diseases in the PNS or CNS, disturbance of the nodes of Ranvier is associated with alteration of paranodal junctions and exposure of juxtaparanodal Kv1 channels that may contribute to neurological disorders. The initiation and propagation of APs in myelinated axons depends on the high concentration of voltage-gated Na+ channels at the AIS and the nodes of Ranvier, respectively. The low-threshold fast-activated Kv1 channels play a highly localized role in shaping the axonal AP at the AIS of cortical pyramidal neurons [26] or in dampening near-threshold excitability in fast-spiking cortical GABAergic interneurons [27], likely depending on Kv1 subunit composition in the different neuronal cell types.
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