Cytosolic sodium regulation in mouse cortical astrocytes and its dependence on potassium and bicarbonate |
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Authors: | Zinnia N. Noor Joachim W. Deitmer Shefeeq M. Theparambil |
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Affiliation: | Abteilung für Allgemeine Zoologie, FB Biologie, University of Kaiserslautern, Kaiserslautern, Germany |
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Abstract: | Sodium plays a major role in different astrocytic functions, including maintenance of ion homeostasis and uptake of neurotransmitters and metabolites, which are mediated by different Na+-coupled transporters. In the current study, the role of an electrogenic sodium-bicarbonate cotransporter (NBCe1), a sodium-potassium-chloride transporter 1 (NKCC1) and sodium-potassium ATPase (Na+-K+-ATPase) for the maintenance of [Na+]i was investigated in cultured astrocytes of wild-type (WT) and of NBCe1-deficient (NBCe1-KO) mice using the Na+-sensitive dye, asante sodium green-2. Our results suggest that cytosolic Na+ was higher in the presence of CO2/HCO3− (15 mM) than CO2/HCO3−-free, HEPES-buffered solution in WT, but not in NBCe1-KO astrocytes (12 mM). Surprisingly, there was a strong dependence of cytosolic [Na+] on the extracellular [HCO3−] attributable to NBCe1 activity. Pharmacological blockage of NKCC1 with bumetanide led to a robust drop in cytosolic Na+ in both WT and NBCe1-KO astrocytes by up to 6 mM. There was a strong dependence of the cytosolic [Na+] on the extracellular [K+]. Inhibition of the Na+-K+-ATPase led to larger increase in cytosolic Na+, both in the absence of K+ as compared with the presence of ouabain and in NBCe1-KO astrocytes as compared with WT astrocytes. Our results show that cytosolic Na+ in mouse cortical astrocytes can vary considerably and depends greatly on the concentrations of HCO3− and K+, attributable to the activity of the Na+-K+-ATPase, of NBCe1 and NKCC1. |
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Keywords: | asante natrium green-2 (ANG-2) sodium-potassium ATPase (Na+-K+-ATPase) sodium-potassium-chloride transporter 1 (NKCC1) sodium potassium chloride cotransporter 1 (NBCe1) |
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