A growing body of literature suggests that certain ion channels participate in fundamental aspects of a cells' biology that are unrelated to electrical signaling. Hence such channels are particularly relevant to non-excitable cells such as glial cells. In this proposal we are examining the role of Ca2+-activated K* channels (KCa), a super-family of ion channels that have the unique ability to translate changes in intracellular Ca2+ to changes in K+ conductance and resting membrane potential. Ca2+ signaling appears to be particularly important in glial cells where propagating waves of activity can be observed in vitro and in vivo under both physiological conditions and in the context of disease and injury. We suggest that KCa channels are a downstream target of Ca2+ waves but also respond to growth factors and cytokines that trigger Ca2+ signals. We suggest in this proposal that KCa channels are of particular importance in glial cells: Wehypothesize that activation of KCa channels is essential in thecoordinated migration of glial cells during brain development,in malignancy and following injury. In this context, KCa channels participate in dynamic shape changes of the glial """"""""invadipodia"""""""" but also play an important role in regulating programmed cells death (apoptosis). We further hypothesize that the function of KCa channels is most pronounced in glial populations that are still migratory and/or proliferative. Upon differentiation these channels are down regulated and replaced by Kir channels that aid in K+ homeostasis in the brain. However, KCa expression and function can be re-acquired in glial cells following acute injury (gliosis) and in disease states in which glial migration is prominent. The latter includes glial derived tumors that invade diffusely into normal brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS031234-18
Application #
7991847
Study Section
Special Emphasis Panel (ZRG1-MDCN-C (02))
Program Officer
Fountain, Jane W
Project Start
1994-03-10
Project End
2013-11-30
Budget Start
2010-12-01
Budget End
2013-11-30
Support Year
18
Fiscal Year
2011
Total Cost
$310,844
Indirect Cost
Name
University of Alabama Birmingham
Department
Neurosciences
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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