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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023375-05
Application #
3406782
Study Section
Physiology Study Section (PHY)
Project Start
1986-04-01
Project End
1994-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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