Neuronscontain distinct functional domains; each specialized at receiving, integratingor propagating information in the form of electrical and chemical signals. Thesedomains can be divided into the dendrites, soma, axon initial segment (AIS), axonand the axon terminals (Rasband, 2011).
This precise neuronal organizationallows the rapid and efficient transmission of action potentials over longdistances. The membrane domains contain a characteristic set ofvoltage-activated ion channels, which define their different functions andshape the electophysiological properties of neurons (Child and Benarroch, 2014). It is not only the types of channels that are critical forthe correct functioning of the nervous system, but also their location andsurface density. Therefore, the clustering, which involves both the sorting andstabilization of these channels in neuronal domains has to be tightly regulated(Ogawa et al., 2010).
In fact, disruption of channeltargeting severely compromises neuronal function, leading to conduction failureand potentially paroxysmal disorders, such as seizures (Child and Benarroch, 2014). Nonetheless, very few of the proteins involved in channelclustering are known and ongoing research is focusing on identifying the exactmolecular composition of the distinct neuronal domains (Rasband, 2011).The aim of this essay is to discuss the current view of the molecular playersunderlying the clustering of voltage-gated potassium channels (VGKC) atspecific axonal regions, the juxtaparanodes (JXP). First, the main subdomainsof myelinated axons will be briefly explained.
Then, the types of VGKC and theirpossible roles will be described. Next, the current understanding of VGKCclustering will be analyzed: first by discussing the theories of channeltrafficking and stabilization and then by reviewing the known molecules constitutingthe VGKC complexes at the JXP. Subsequently, a new hypothesis on the moleculesinvolved in VGKC clustering will be considered and finally, their clinical significancewill be explained.