&lt;sup&gt;31&lt;/sup&gt;P Nuclear Magnetic Resonance and Saturation Transfer Studies of the Isolated Perfused Rat Kidney

Dowd, Terry L.; Barac‐Nieto, Mario; Gupta, Raj K.; Spitzer, Adrian

doi:10.1159/000173190

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…The cytoplasmic concentration of ATP ([ATP] c ) at steady state is computed as 2.5 mM, in good agreement with measured values (1.5-2.8 mM) in rat renal tissue (23,61). The predicted [P i ] c (1.7 mM) also falls within the published range of values (1-10 mM) (1,23,32,61), and the predicted ATP-to-ADP cytoplasmic concentration ratio ([ATP] c /[ADP] c ), 10.9, is comparable to that measured (~9) in mouse PTs (99). Freeman and colleagues (31) reported a P/O of 1.7-2.0 for the whole kidney in vivo (32) and 2.5 in the perfused kidney, and the model value (2.0) lies within these measured values.…”

Section: Mitochondria In Vivosupporting

confidence: 81%

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A model of mitochondrial O₂consumption and ATP generation in rat proximal tubule cells

Edwards

Palm

2020

American Journal of Physiology-Renal Physiology

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Oxygen tension in the kidney is mostly determined by O2 consumption (Qo2), which is, in turn, closely linked to tubular Na+ reabsorption. The objective of the present study was to develop a model of mitochondrial function in the proximal tubule (PT) cells of the rat renal cortex to gain more insight into the coupling between Qo2, ATP formation (GATP), ATP hydrolysis (QATP), and Na+ transport in the PT. The present model correctly predicts in vitro and in vivo measurements of Qo2, GATP, and ATP and Pi concentrations in PT cells. Our simulations suggest that O2 levels are not rate limiting in the proximal convoluted tubule, absent large metabolic perturbations. The model predicts that the rate of ATP hydrolysis and cytoplasmic pH each substantially regulate the GATP-to-Qo2 ratio, a key determinant of the number of Na+ moles actively reabsorbed per mole of O2 consumed. An isolated increase in QATP or in cytoplasmic pH raises the GATP-to-Qo2 ratio. Thus, variations in Na+ reabsorption and pH along the PT may, per se, generate axial heterogeneities in the efficiency of mitochondrial metabolism and Na+ transport. Our results also indicate that the GATP-to-Qo2 ratio is strongly impacted not only by H+ leak permeability, which reflects mitochondrial uncoupling, but also by K+ leak pathways. Simulations suggest that the negative impact of increased uncoupling in the diabetic kidney on mitochondrial metabolic efficiency is partly counterbalanced by increased rates of Na+ transport and ATP consumption. This model provides a framework to investigate the role of mitochondrial dysfunction in acute and chronic renal diseases.

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Section: Mitochondria In Vivosupporting

confidence: 81%

“…The initial values of the cytoplasmic concentration of succinate and phosphate creatine are taken from Horn et al (48) and Toma et al (90). The total concentration of adenosine phosphate species (ATP ϩ ADP ϩ AMP) is set to 2.75 mM (23,61). Other initial values are those of the original model (96).…”

Section: Model Parametersmentioning

confidence: 99%

A model of mitochondrial O₂consumption and ATP generation in rat proximal tubule cells

Edwards

Palm

2020

American Journal of Physiology-Renal Physiology

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“…The mitochondrial electrical potential gradient was predicted to be 155 mV, in the interior of known range from 150 to 180 mV [9]. Typical measured ranges for the concentration of ATP vary widely from 1.3 to 2.8 mM [15, 54]. The ATP/ADP ratio has been measured to be roughly 9 in mice renal cortex [87], however Zager notes that the ratio is extremely variable.…”

Section: Resultsmentioning

confidence: 99%

A Mathematical Model of Mitochondria in Proximal Tubule and Thick Ascending Limb Cells

Bell

2021

Preprint

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Mitochondria are a key player in several kinds of tissue injury, and are even the ultimate cause of certain diseases. In this work we introduce new models of mitochondrial ATP generation in multiple tissues, including liver hepatocytes and the medullary thick ascending limb in the kidney. Using this model, we predict these tissues' responses to hypoxia, uncoupling, ischemia-reperfusion, and oxidative phosphorylation dysfunction. Our results suggest mechanisms explaining differences in robustness of mitochondrial function across tissues. The medullary thick ascending limb and proximal tubule in the kidney both experience a high metabolic demand, while having lower baseline activity of oxidative phosphorylation relative to the liver. These factors make these tissues susceptible to dysfunction of Complex III. A lower baseline oxygen tension observed in the thick ascending limb makes it susceptible to Complex IV. On the other hand, since the liver lacks these risk factors, and has higher baseline rates of glycolysis, it is less susceptible to all kinds of oxidative phosphorylation dysfunction.

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NMR studies of phosphate metabolism in the isolated perfused kidney of developing rats

1990

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During growth, the capacity for renal phosphate (Pi) reabsorption varies as a function of Pi demand. These changes occur in the absence of changes in extracellular concentration of Pi and are also observed in renal cells cultured in defined media. These findings suggest a direct regulatory effect of intracellular Pi on its transport systems. We postulate that a low intracellular Pi concentration [( Pi]i) occurs in the developing kidney as a consequence of differences in Pi metabolism between growing and mature cells and that a low [Pi]i, in turn, leads to adaptive changes in renal Pi transport. In order to assess this hypothesis, we used 31P-nuclear magnetic resonance (NMR) to measure the intracellular concentrations of NMR-visible Pi and phospho-metabolites and the rates of Pi turnover due to adenosine triphosphate (ATP) synthesis, in isolated perfused kidneys of 3- to 4-week-old and 12- to 13-week-old rats. The [Pi]i was lower (1.7 +/- 0.1 vs 2.7 +/- 0.1 mM, P less than 0.05) in kidneys of growing than of adult rats, while the ATP (2.9 +/- 0.3 vs 2.8 +/- 0.5 mM) and adenosine diphosphate (ADP) (-0.2 mM) concentrations were similar at the two ages, consistent with a high phosphorylation potential in the kidneys of the younger animals. Radiofrequency irradiation of the gamma-P of ATP resulted in reduction in the intensity of the Pi resonance of 62 +/- 5% in the newborn and 38 +/- 3% in the adult (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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<sup>31</sup>P Nuclear Magnetic Resonance and Saturation Transfer Studies of the Isolated Perfused Rat Kidney

Cited by 5 publications

References 14 publications

A model of mitochondrial O₂consumption and ATP generation in rat proximal tubule cells

A model of mitochondrial O₂consumption and ATP generation in rat proximal tubule cells

A Mathematical Model of Mitochondria in Proximal Tubule and Thick Ascending Limb Cells

NMR studies of phosphate metabolism in the isolated perfused kidney of developing rats

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<sup>31</sup>P Nuclear Magnetic Resonance and Saturation Transfer Studies of the Isolated Perfused Rat Kidney

Cited by 5 publications

References 14 publications

A model of mitochondrial O2consumption and ATP generation in rat proximal tubule cells

A model of mitochondrial O2consumption and ATP generation in rat proximal tubule cells

A Mathematical Model of Mitochondria in Proximal Tubule and Thick Ascending Limb Cells

NMR studies of phosphate metabolism in the isolated perfused kidney of developing rats

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A model of mitochondrial O₂consumption and ATP generation in rat proximal tubule cells

A model of mitochondrial O₂consumption and ATP generation in rat proximal tubule cells