IONIC CHANNELS IN MYELINATED NERVES

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Excitable ion channels (Na+ and K+), of the types classically involved in nerve impulse generation, and present on both the axons and the ensheathing glial cells in the mammalian peripheral nervous system. The long-term goal is to elucidate the role of ion channels, particularly their plasticity in both axons and glia, in normal and abnormal axo-glial interactions with special emphasis on demyelinating diseases. The specific aims of this proposal focus on the plasticity of glial ion channels and its relation to two cellular behaviors of mammalian Schwann cells, namely, proliferation and myelinogenesis. Plasticity in glial channel expression will be measured with the patch-clamp on Schwann cell whose myelinogenic and proliferative behaviors are altered either genetically (neurological mutants), by glial mitogens in tissue culture, or by other experimental perturbations of the axo-glial relations, (demyelination, remyelination, regeneration and nerve-grafting). Functional links between glial channels and cellular responses will be examined with ion channel blockers and fluorescent probes for monitoring trafficking of intracellular ions. The issue of axonal regulation of glial channels, germane to the speculation of a glia-to-axon transfer of excitable ion channels, will be explored. The specific hypothesis to be tested is that up-regulation of glial K channels is linked functionally to proliferation, and that down-regulation of excitable glial channels is associated with normal myelinogenesis.