Ion channel sequestration in central nervous system axons

Na+ and K+ channel localization and clustering are essential for proper ele ctrical signal generation and transmission in CNS myelinated nerve fibres. In particular, Na+ channels are clustered at high density at nodes of Ranvi er, and Shaker-type K+ channels are sequestered in juxtaparanodal zones, ju st beyond the paranodal axoglial junctions. The mechanisms of channel local ization at nodes of Ranvier in the CNS during development in both normal an d hypomyelinating mutant animals are discussed and reviewed. As myelination proceeds, Na+ channels are initially found in broad zones within gaps betw een neighbouring oligodendroglial processes, and thm are condensed into foc al clusters. This process appears to del,end on the formation of axoglial j unctions. K+ channels are first detected in juxtaparanodal zones, and in mu tant mice lacking normal axoglial junctions, these channels fail to cluster . In these mice, despite the presence of numerous oligodendrocytes, Na+ cha nnel dusters are rare, and when present, are highly irregular. A number of molecules have recently been described that are candidates for a role in th e neuron-glial interactions driving ion channel clustering. This paper revi ews the cellular and molecular events responsible for formation of the matu re node of Ranvier in the CNS.