Ion channel sequestration in central nervous system axons

Na+ and K+ channel localization and clustering are essential for proper electrical signal generation and transmission in CNS myelinated nerve fibres. In particular, Na+ channels are clustered at high density at nodes of Ranvier, and Shaker-type K+ channels are sequestered in juxtaparanodal zones, just beyond the paranodal axoglial junctions. The mechanisms of channel localization at nodes of Ranvier in the CNS during development in both normal and hypomyelinating mutant animals are discussed and reviewed. As myelination proceeds, Na+ channels are initially found in broad zones within gaps between neighbouring oligodendroglial processes, and then are condensed into focal clusters. This process appears to depend on the formation of axoglial junctions. K+ channels are first detected in juxtaparanodal zones, and in mutant mice lacking normal axoglial junctions, these channels fail to cluster. In these mice, despite the presence of numerous oligodendrocytes, Na+ channel clusters are rare, and when present, are highly irregular. A number of molecules have recently been described that are candidates for a role in the neuron-glial interactions driving ion channel clustering. This paper reviews the cellular and molecular events responsible for formation of the mature node of Ranvier in the CNS.