Hippocampal (HC) neurons exist in two populations based on initial intracellular pH (pHi); one consisting of neurons with low initial pHi values and the other with high initial pHi values. High-pHi neurons recover faster from acid loads than do low-pHi neurons. There are two specific aims: (1) to explore the molecular basis of low- vs. high-pHi neurons and determine whether the difference relates to neurotransmitter content and/or properties of specific HCO3 transporters expressed by a neuron. The approach will be to monitor pHi in HC neurons grown on gridded coverslips and assess activities of HCO3 transporters in identified cells. Immunocytochemistry and single-cell PCR will be used to assess molecular phenotype in the same cells. A knockdown technique will show how the expression of specific HCO3 transporters affects the low/high pHi state. (2) To use chronic hypoxia, and the return to normoxia, as tools to shift the low- vs. high-pHi status of HC neurons. The approach will be to monitor individual neurons. The results from these studies are significant because the pHi differences between low- and high-pHi neurons are large enough to have a major impact on neuronal activity. In other words, pHi shifts could be a form of neuromodulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS053199-01
Application #
6998615
Study Section
Special Emphasis Panel (ZRG1-F03B (20))
Program Officer
Talley, Edmund M
Project Start
2005-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$48,296
Indirect Cost
Name
Yale University
Department
Physiology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Liu, Y; Xu, K; Chen, L M et al. (2010) Distribution of NBCn2 (SLC4A10) splice variants in mouse brain. Neuroscience 169:951-64
Chen, L-M; Kelly, M L; Parker, M D et al. (2008) Expression and localization of Na-driven Cl-HCO(3)(-) exchanger (SLC4A8) in rodent CNS. Neuroscience 153:162-74