The sodium channel is a transmembrane protein that mediates the voltage dependent sodium permeability of electrically excitable membranes. Its presence is of obvious importance for the generation and propagation of action potentials along axolemma. Using well characterized antibodies directed against sodium channels and immunocytochemical/radioimmunoassay methods, we plan to study separately how experimental demyelination and aging affect sodium channels in nervous tissues. In the first set of observations we will determine and contrast sodium channel distribution and quantity along peripheral nerve axons demyelinated acutely with potassium tellurite, subacutely with tunicamycin, and chronically with doxorubicin. These studies should help us understand how demyelinated axons become remodelled to re-establish conduction. Such information is important since the resumption of axonal conduction appears to be the basis for recovery in many human demyelinating diseases. In the second set of observations we will determine sodium channel distribution and quantity in aged nervous tissue and contrast this with their distribution and quantity in young nervous tissue. An established and well studied aging rat colony will provide ample aged brain and peripheral nerve for one part of this study. In a separate series of observations we will examine sodium channels in human brain tissue affected by diseases associated with aging. A special interest will be the examination of postmortem brain afflicted with Alzheimer's disease. These studies should reveal whether aging per se or diseases associated with aging result in biochemically detectable changes in sodium channels that could culminate in neuronal dysfunction. Such information is important since little is known regarding the mechanisms by which aging or diseased neurons lose their ability to function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG009417-02
Application #
3790415
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
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