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Relationship: 1811
Title
Decreased Na/K ATPase activity leads to Decreased proximal tubular vectorial transport
Upstream event
Downstream event
Key Event Relationship Overview
AOPs Referencing Relationship
AOP Name | Adjacency | Weight of Evidence | Quantitative Understanding | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|---|---|
Inhibition of complex I of the electron transport chain leading to chemical induced Fanconi syndrome | adjacent | Not Specified | Not Specified | Evgeniia Kazymova (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Sex Applicability
Life Stage Applicability
Key Event Relationship Description
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 Collection Strategy
Evidence Supporting this KER
Biological Plausibility
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
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
Known modulating factors
Quantitative Understanding of the Linkage
Response-response Relationship
Time-scale
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
References
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