Assembly and Function of the Juxtaparanodal Kv1 Complex in Health and Disease

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.

Automated summary

The distribution of specific potassium channels in axons plays a crucial role in maintaining the shape and frequency of action potentials in myelinated fibers. Kv1 channels at the axon initial segment have a significant impact on spike initiation and waveform, while their role at the juxtaparanodes is not fully understood. Exposure of Kv1 channels in demyelinating neuropathy results in altered saltatory conduction.