ArticleAmerican journal of physiology. Renal physiology2010
A mathematical model of rat ascending Henle limb. II. Epithelial function.
Article in American journal of physiology. Renal physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 37 citations in OpenAlex.
- Flow-dependent transport processes 2024: filtration, absorption, and secretion.American journal of physiology. Renal physiology · 2025Article
- A brief history of the cortical thick ascending limb: a systems-biology perspective.American journal of physiology. Renal physiology · 2025Review
- Directing two-way traffic in the kidney: A tale of two ions.The Journal of general physiology · 2022Article
- Kidney metabolism and acid-base control: back to the basics.Pflugers Archiv : European journal of physiology · 2022Review
- A mathematical model of the rat kidney. IV. Whole kidney response to hyperkalemia.American journal of physiology. Renal physiology · 2022Article
- A mathematical model of the rat kidney. III. Ammonia transport.American journal of physiology. Renal physiology · 2021Article
- A mathematical model of the rat kidney. II. Antidiuresis.American journal of physiology. Renal physiology · 2020Article
- Pulsatile flow through idealized renal tubules: Fluid-structure interaction and dynamic pathologies.Mathematical biosciences and engineering : MBE · 2019Article
- A mathematical model of the rat kidney: KAmerican journal of physiology. Renal physiology · 2017Article
- Ammonia Transporters and Their Role in Acid-Base Balance.Physiological reviews · 2017Review
- A new microscope for the kidney: mathematics.American journal of physiology. Renal physiology · 2017Article
- Recent advances in renal hemodynamics: insights from bench experiments and computer simulations.American journal of physiology. Renal physiology · 2015Review
- Simulation of Cl(-) Secretion in Epithelial Tissues: New Methodology Estimating Activity of Electro-Neutral Cl(-) Transporter.Frontiers in physiology · 2015Article
- Effects of NKCC2 isoform regulation on NaCl transport in thick ascending limb and macula densa: a modeling study.American journal of physiology. Renal physiology · 2014Article
- Computer model of unstirred layer and intracellular pH changes. Determinants of unstirred layer pH.Journal of biological physics · 2013Article
- Fluid dilution and efficiency of Na(+) transport in a mathematical model of a thick ascending limb cell.American journal of physiology. Renal physiology · 2013Article
- Transport efficiency and workload distribution in a mathematical model of the thick ascending limb.American journal of physiology. Renal physiology · 2013Article
- Renal ammonia metabolism and transport.Comprehensive Physiology · 2013Review
- Development of a physiologically based computational kidney model to describe the renal excretion of hydrophilic agents in rats.Frontiers in physiology · 2012Article
- Potassium deprivation: a systems approach.American journal of physiology. Renal physiology · 2011Article
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2 authors at 2 institutions in 1 country.
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Abstract
A mathematical model of ascending Henle limb (AHL) epithelium has been fashioned using kinetic representations of Na+-K+-2Cl- cotransporter (NKCC2), KCC4, and type 3 Na+/H+ exchanger (NHE3), with transporter densities selected to yield the reabsorptive Na+ flux expected for rat tubules in vivo. Of necessity, this model predicts fluxes that are higher than those measured in vitro. The kinetics of the NKCC and KCC are such that Na+ reabsorption by the model tubule is responsive to variation in luminal NaCl concentration over the range of 30 to 130 mM, with only minor changes in cell volume. Peritubular KCC accounts for about half the reabsorptive Cl- flux, with the remainder via peritubular Cl- channels. Transcellular Na+ flux is turned off by increasing peritubular KCl, which produces increased cytosolic Cl- and thus inhibits NKCC2 transport. In the presence of physiological concentrations of ammonia, there is a large acid challenge to the cell, due primarily to NH4+ entry via NKCC2, with diffusive NH3 exit to both lumen and peritubular solutions. When NHE3 density is adjusted to compensate this acid challenge, the model predicts luminal membrane proton secretion that is greater than the HCO3(-)-reabsorptive fluxes measured in vitro. The model also predicts luminal membrane ammonia cycling, with uptake via NKCC2 or K+ channel, and secretion either as NH4+ by NHE3 or as diffusive NH3 flux in parallel with a secreted proton. If such luminal ammonia cycling occurs in vivo, it could act in concert with luminal K+ cycling to facilitate AHL Na+ reabsorption via NKCC2. With physiological ammonia, peritubular KCl also blunts NHE3 activity by inhibiting NH4+ uptake on the Na-K-ATPase, and alkalinizing the cell.
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