Energy metabolism and ion transport studied in single neurons

Energy metabolism, ion transport, and water content are interrelated in mechanisms of homeostasis of the brain intracellular and extracellular environment. The simplest model of cell homeostasis, the pump–leak hypothesis, incorporates basic relationships between these variables. Although this model accurately calculates steady-state cell volumes, ion concentrations, and metabolic rates, it fails to predict dynamic changes in these properties during elevated extracellular potassium, metabolic inhibition, and osmotic swelling. We have investigated relationships between ions, energy metabolism, and water content in cerebral astrocytes cultured from the neonatal rat. These cells swell more in hypoosmotic phosphate-buffered saline (PBS) containing NaCl than in hypoosmotic PBS with all NaCl replaced equiosmotically by sucrose. Unidirectional Na+ influx also is greater in cells suspended in hypoosmotic, compared with isoosmotic PBS. These data suggest that astrocytes possess a cell volume dependent mechanism of Na+ accumulation. The influx of Na+ during swelling may be coupled to metabolism via Na–K ATPase and may contribute to the sustained swelling of astrocytes observed in hypoosmotic swelling of the brain in situ.Key words: sodium, hypoosmolality, sodium–potassium adenosine triphosphatase, mathematical modeling.

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Phosphorylation of Na+,K+-ATPase at Tyr10 of the α1-Subunit is Suppressed by AMPK and Enhanced by Ouabain in Cultured Kidney Cells

The Journal of Membrane Biology ◽

10.1007/s00232-021-00209-7 ◽

2021 ◽

Author(s):

Metka Petrič ◽

Anja Vidović ◽

Klemen Dolinar ◽

Katarina Miš ◽

Alexander V. Chibalin ◽

...

Keyword(s):

Energy Metabolism ◽

Ion Transport ◽

Tyrosine Kinases ◽

Egf Receptor ◽

Ion Homeostasis ◽

Lactate Production ◽

Serine Phosphorylation ◽

Whole Body ◽

Dependent Manner ◽

Α1 Subunit

AbstractNa+,K+-ATPase (NKA) is essential for maintenance of cellular and whole-body water and ion homeostasis. In the kidney, a major site of ion transport, NKA consumes ~ 50% of ATP, indicating a tight coordination of NKA and energy metabolism. AMP-activated protein kinase (AMPK), a cellular energy sensor, regulates NKA by modulating serine phosphorylation of the α1-subunit, but whether it modulates other important regulatory phosphosites, such as Tyr10, is unknown. Using human kidney (HK-2) cells, we determined that the phosphorylation of Tyr10 was stimulated by the epidermal growth factor (EGF), which was opposed by inhibitors of Src kinases (PP2), tyrosine kinases (genistein), and EGF receptor (EGFR, gefitinib). AMPK activators AICAR and A-769662 suppressed the EGF-stimulated phosphorylation of EGFR (Tyr1173) and NKAα1 at Tyr10. The phosphorylation of Src (Tyr416) was unaltered by AICAR and increased by A-769662. Conversely, ouabain (100 nM), a pharmacological NKA inhibitor and a putative adrenocortical hormone, enhanced the EGF-stimulated Tyr10 phosphorylation without altering the phosphorylation of EGFR (Tyr1173) or Src (Tyr416). Ouabain (100–1000 nM) increased the ADP:ATP ratio, while it suppressed the lactate production and the oxygen consumption rate in a dose-dependent manner. Treatment with ouabain or gene silencing of NKAα1 or NKAα3 subunit did not activate AMPK. In summary, AMPK activators and ouabain had antagonistic effects on the phosphorylation of NKAα1 at Tyr10 in cultured HK-2 cells, which implicates a role for Tyr10 in coordinated regulation of NKA-mediated ion transport and energy metabolism. Graphical Abstract

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Relative effects of furosemide and ethacrynic acid on ion transport and energy metabolism in slices of rat kidney-cortex

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/bf00506264 ◽

1981 ◽

Vol 317 (1) ◽

pp. 90-96 ◽

Cited By ~ 14

Author(s):

G. D. V. van Rossum ◽

S. A. Ernst ◽

M. A. Russo

Keyword(s):

Energy Metabolism ◽

Ion Transport ◽

Ethacrynic Acid ◽

Rat Kidney ◽

Kidney Cortex ◽

Rat Kidney Cortex

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4.7 Ion Transport and Energy Metabolism

Handbook of Neurochemistry and Molecular Neurobiology ◽

10.1007/978-0-387-30411-3_16 ◽

2007 ◽

pp. 429-465 ◽

Cited By ~ 1

Author(s):

O. Vergun ◽

K. E. Dineley ◽

I. J. Reynolds

Keyword(s):

Energy Metabolism ◽

Ion Transport

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Cell Biology of Reef-Building Corals: Ion Transport, Acid/Base Regulation, and Energy Metabolism

Acid-Base Balance and Nitrogen Excretion in Invertebrates ◽

10.1007/978-3-319-39617-0_7 ◽

2016 ◽

pp. 193-218 ◽

Cited By ~ 9

Author(s):

Martin Tresguerres ◽

Katie L. Barott ◽

Megan E. Barron ◽

Dimitri D. Deheyn ◽

David I. Kline ◽

...

Keyword(s):

Energy Metabolism ◽

Ion Transport ◽

Cell Biology ◽

Acid Base

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Ion transport in gills of the euryhaline fish Gillichthys mirabilis is facilitated by a phosphocreatine circuit

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.4.r1003 ◽

1995 ◽

Vol 268 (4) ◽

pp. R1003-R1012 ◽

Cited By ~ 7

Author(s):

D. Kultz ◽

G. N. Somero

Keyword(s):

Energy Metabolism ◽

Ion Transport ◽

Plasma Osmolality ◽

Gill Tissue ◽

Functional Coupling ◽

Gillichthys Mirabilis ◽

Energy Demands ◽

Atp Concentration ◽

Order Of Magnitude ◽

Active Ion Transport

The function of creatine kinase (CK) isozymes in energy metabolism and the short-term regulation of active ion transport in gills of the euryhaline teleost Gillichthys mirabilis was investigated. After a transfer of fish from regular seawater [36 parts/thousand (ppt)] to hypersaline water (60 ppt), the plasma osmolality increased significantly from 361.0 +/- 5.2 to 434.2 +/- 20.6 mosmol/kgH2O within 2 h and was regulated down to 391.8 +/- 11.3 mosmol/kgH2O within 12 h. Although the ATP concentration in the gill tissue remained unchanged, the creatine concentration increased significantly from 17.3 +/- 3.2 to 37.6 +/- 5.9 nmol/mg protein within 2 h after the salinity change. CK and Na(+)-K(+)-adenosinetriphosphatase-(Na(+)-K(+)-ATPase) activities were unchanged 48 h after transfer. Independent of salinity, the activities of CK were three to seven times those of the Na(+)-K(+)-ATPase, and the creatine concentration in the gill was at least one order of magnitude higher than the ATP concentration. The occurrence of muscle-type CK (CK-M), brain-type CK, and mitochondrial CK was demonstrated. CK-M was predominant in gills (59 +/- 7.1% of total CK activity). Evidence for a direct functional coupling between CK and Na(+)-K(+)-ATPase was obtained with permeabilized gill cells, by using the CK inhibitor iodoacetamide, which abolishes the competitive channeling of ADP from the external pyruvate kinase reaction to the endogeneous CK reaction in a coupled in situ Na(+)-K(+)-ATPase assay. Our results show the significance and the central regulatory role for energy metabolism and adaptive ionoregulation of a phosphocreatine-CK circuit in situations of high and fluctuating energy demands for euryhaline fishes.

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