Microglia are a hematopoetic-derived population of cells that make up 20% of the non-neuronal cells in the brain, and function both as neuronal support and as the macrophage-like resident immune cells. During acute brain pathology, substances secreted by damaged or dying cells can cause activation of microglia resulting in microglia-orchestrated neuroinflammation that can exacerbate pathological brain damage. We hypothesize that ion channel function is involved in microglia activation by maintaining membrane potential (Vm) and/or promoting dynamic, oscillatory changes in Vm. This hypothesis is based on our laboratory's finding that blocking specific ion channels inhibits microglia activation, and on my results showing that the same channels promote Vm oscillations. In this proposal, I will use electrophysiological, several types of single-cell flourescence imaging, and cellular functional assays to assess the role of Vm in microglia activation. In particular, I will focus on intracellular calcium regulation and chemotaxis. The ultimate goal of our studies is to gain an understanding of how to regulate microglia activation, possibly leading to novel treatment of brain pathologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS049742-02X1
Application #
7118461
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Nunn, Michael
Project Start
2004-09-15
Project End
2006-09-14
Budget Start
2005-09-15
Budget End
2006-09-14
Support Year
2
Fiscal Year
2005
Total Cost
$2,750
Indirect Cost
Name
University Health Network
Department
Type
DUNS #
208469486
City
Toronto
State
ON
Country
Canada
Zip Code
M5 2-M9
Schlichter, Lyanne C; Jiang, Jiahua; Wang, John et al. (2014) Regulation of hERG and hEAG channels by Src and by SHP-1 tyrosine phosphatase via an ITIM region in the cyclic nucleotide binding domain. PLoS One 9:e90024
Newell, Evan W; Stanley, Elise F; Schlichter, Lyanne C (2007) Reversed Na+/Ca2+ exchange contributes to Ca2+ influx and respiratory burst in microglia. Channels (Austin) 1:366-76
Ducharme, Guillaume; Newell, Evan W; Pinto, Crystal et al. (2007) Small-conductance Cl- channels contribute to volume regulation and phagocytosis in microglia. Eur J Neurosci 26:2119-30