Regulation of intracellular pH by electrogenic Na+/HCO3-co-transporters in embryonic neural stem cell-derived radial glia-like cells

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Nordström , T , Andersson , L C & Åkerman , K E O 2019 , ' Regulation of intracellular pH by electrogenic Na+/HCO3-co-transporters in embryonic neural stem cell-derived radial glia-like cells ' , Biochimica et Biophysica Acta. Biomembranes , vol. 1861 , no. 6 , pp. 1037-1048 . https://doi.org/10.1016/j.bbamem.2019.03.007

Title: Regulation of intracellular pH by electrogenic Na+/HCO3-co-transporters in embryonic neural stem cell-derived radial glia-like cells
Author: Nordström, Tommy; Andersson, Leif C.; Åkerman, Karl E. O.
Contributor: University of Helsinki, Medicum
University of Helsinki, Department of Pathology
University of Helsinki, Medicum
Date: 2019-06-01
Language: eng
Number of pages: 12
Belongs to series: Biochimica et Biophysica Acta. Biomembranes
ISSN: 0005-2736
URI: http://hdl.handle.net/10138/304039
Abstract: A stroke causes a hypoxic brain microenvironment that alters neural cell metabolism resulting in cell membrane hyperpolarization and intracellular acidosis. We studied how intracellular pH (pH(i)) is regulated in differentiated mouse neural progenitor cells during hyperpolarizing conditions, induced by prompt reduction of the extra cellular K+ concentration. We found that the radial glia-like population in differentiating embryonic neural progenitor cells, but not neuronal cells, was rapidly acidified under these conditions. However, when extra cellular calcium was removed, an instant depolarization and recovery of the pH(i), back to normal levels, took place. The rapid recovery phase seen in the absence of calcium, was dependent on extracellular bicarbonate and could be inhibited by 50859, a potent Na/HCO3 cotransporter inhibitor. Immunostaining and PCR data, showed that NBCe1 (SLC4A4) and NBCn1 (SLC4A7) were expressed in the cell population and that the pH(i) recovery in the radial glial-like cells after calcium removal was mediated mainly by the electrogenic sodium bicarbonate transporter NBCe1 (SLC4A4). Our results indicate that extracellular calcium might hamper pH(i) regulation and Na/HCO3 cotransporter activity in a brain injury microenvironment. Our findings show that the NBC-type transporters are the main pH(i) regulating systems prevailing in glia-like progenitor cells and that these calcium sensitive transporters are important for neuronal progenitor cell proliferation, survival and neural stem cell differentiation.
Subject: Neurosphere
Stem cell
Na+/HCO3- co-transporter
pH
Hyperpolarization
Calcium
GLUTAMATE RELEASE
RAT-BRAIN
NEUROGENESIS
NEURONS
PROLIFERATION
ACIDOSIS
HYPOXIA
HYPOKALEMIA
COTRANSPORT
MODULATION
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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