API

Relationship: 1811

Title

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Decreased Na/K ATPase activity leads to Decreased proximal tubular vectorial transport

Upstream event

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Decreased Na/K ATPase activity

Downstream event

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Decreased proximal tubular vectorial transport

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Adjacency Weight of Evidence Quantitative Understanding
Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome adjacent Not Specified Not Specified

Taxonomic Applicability

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Sex Applicability

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Life Stage Applicability

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Key Event Relationship Description

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The sodium/potassium (Na/K) ATPase consumes ATP to build up a sodium gradient that is the driving force for most of the proximal tubular reabsorption operated by secondary active transporters exchanging sodium for glucose, amino acids, phosphate or other ions (Jørgensen, 1986). When the ATP supply is reduced in the cell, the Na/K ATPase cannot function properly, and subsequent secondary active transports are reduced.

Evidence Supporting this KER

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Biological Plausibility

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The dependence of proximal tubule reabsorption on the sodium gradient built by the Na/K ATPase is one of the key aspects of proximal tubular physiology (Jørgensen, 1986; Schafer, Troutman, Watkins, & Andreoli, 1981).

Empirical Evidence

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Inhibition of the Na/K ATPase activity by addition of the inhibitor ouabain causes a reduction in apical to basolateral net volume reabsorption in isolated rabbit renal cortex tubule segments (Schafer et al., 1981).

Uncertainties and Inconsistencies

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Quantitative Understanding of the Linkage

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Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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Jørgensen, P. L. (1986). Structure, function and regulation of Na,K-ATPase in the kidney. Kidney International, 29(1), 10–20. https://doi.org/10.1038/KI.1986.3

Schafer, J. A., Troutman, S. L., Watkins, M. L., & Andreoli, T. E. (1981). Flow dependence of fluid transport in the isolated superficial pars recta: evidence that osmotic disequilibrium between external solutions drives isotonic fluid absorption. Kidney International, 20(5), 588–97. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7343709