Completion of myelin compaction, but not the attachment of oligodendroglial processes triggers K+ channel clustering

Abstract

The characteristic localization of ion channels is crucial for the propagation of saltatory conduction in myelinated nerves. Voltage-gated Na(+) channels are located at nodes of Ranvier while voltage-gated K(+) channels are mainly found at juxtaparanodal regions. Recently, a humoral factor secreted by oligodendrocytes has been reported to induce clustering of Na(+) channels in CNS axons. However, the molecular mechanisms for K(+) channel clustering as well as the role of oligodendrocytes are still uncertain. To clarify whether myelin sheath itself can induce the distinct distribution of K(+) channels, we have investigated the localization of K(+) channels in adult and developing mouse optic nerves. The CNS axons from chronic demyelinating and hypomyelinating mice were also examined to determine if myelin sheaths were required for the maintenance of clusters. In all cases, the K(+) channel clustering correlated well with compact myelin, but not with the presence of oligodendrocytes, suggesting that, in contrast to Na(+) channel clustering, the formation of compact myelin is required for initiation as well as maintenance of K(+) channel clustering. In addition, postsynaptic density protein-95 (PSD-95) or its highly related protein was found colocalized with K(+) channels, suggesting that it may interact with K(+) channels to form clusters at juxtaparanodal regions.

Myelination of Congenitally Dysmyelinated Spinal Cord Axons by Adult Neural Precursor Cells Results in Formation of Nodes of Ranvier and Improved Axonal Conduction

“…The differential impact of myelination on Caspr and Kv1.2 subunit restoration may reflect different signaling mechanisms for their localization along axons. Although K ϩ channel juxtaparanodal localization is dictated by compact myelin, as was suggested previously (Baba et al, 1999), the formation of axoglial junctions is sufficient for Caspr paranodal localization. Reorganization of Caspr immunostaining in our studies sug- Figure 8.…”

Effects of K+ Channel Blockers on Developing Rat Myelinated CNS Axons: Identification of Four Types of K+Channels

“…Immunocytologic detection of Kv channels in the optic nerves has been performed so far only after P10 -P14 (Baba et al 1999;Rasband et al 1998Rasband et al , 1999 when the K ϩ channels are densely packed in juxtaparanodal regions. The present pharmacological data made it possible to identify DTX-I-sensitive channels at earlier ages (as early as P1) and to establish that the effects of DTX-I and KTX peak at around P12.…”

“…Only two types of K ϩ channels have been pharmacologically identified so far to our knowledge in the adult rat optic nerve using this technique: one of these is sensitive to 4-AP and the other is sensitive to TEA . Based on immunocytologic detection data, Baba et al (1999) have reported that Kv1.1 and Kv1.2 ␣ subunits are diffusely distributed in mouse optic nerves at P10 and are sequestrated in juxtaparanodal regions during development. However, no electrophysiological studies were attempted to identify the variations in K ϩ expression during development and to compare the K ϩ channels present in CNS and PNS fibers.…”

Spatiotemporal Expression of PSD-95 and nNOS After Rat Sciatic Nerve Injury

“…Additionally, there is a few colocalization between PSD-95 and NF-200 expressed in axons. As an attractive candidate for an axonal Kv1 channel binding partner, PSD-95 exhibits a high affinity interaction with the class I PDZbinding peptide motifs at the COOH termini of Kv1.1, Kv1.2, and Kv1.4 [24], suggesting that PSD-95 might be responsible for the clustering of Kv 1 channels at juxtaparanodes of myelinated axons [32,44].…”