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Cytosolic sodium regulation in mouse cortical astrocytes and its dependence on potassium and bicarbonate
Author(s) -
Noor Zinnia N.,
Deitmer Joachim W.,
Theparambil Shefeeq M.
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26824
Subject(s) - cotransporter , sodium , cytosol , bicarbonate , chemistry , potassium , extracellular , bumetanide , homeostasis , ouabain , biochemistry , biophysics , medicine , endocrinology , biology , enzyme , organic chemistry
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 CO 2 /HCO 3 − (15 mM) than CO 2 /HCO 3 − ‐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 [HCO 3 − ] 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 HCO 3 − and K + , attributable to the activity of the Na + ‐K + ‐ATPase, of NBCe1 and NKCC1.