ArticleAmerican journal of physiology. Renal physiology2010
A mathematical model of rat ascending Henle limb. I. Cotransporter 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 19 papers.
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Who cites it
19 citing papers in PubMed.
- 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
- A mathematical model of the rat kidney. III. Ammonia transport.American journal of physiology. Renal physiology · 2021Article
- Pulsatile flow through idealized renal tubules: Fluid-structure interaction and dynamic pathologies.Mathematical biosciences and engineering : MBE · 2019Article
- Physiological roles and molecular mechanisms of KThe Journal of physiology · 2019Review
- Mathematical model reveals role of nucleotide signaling in airway surface liquid homeostasis and its dysregulation in cystic fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The renal cortical collecting duct: a secreting epithelium?The Journal of physiology · 2016Article
- Mechanisms of astrocytic K(+) clearance and swelling under high extracellular K(+) concentrations.The journal of physiological sciences : JPS · 2016Article
- Parameter estimation for mathematical models of a nongastric H+(Na+)-K(+)(NH4+)-ATPase.American journal of physiology. Renal physiology · 2015Article
- Simulation of Cl(-) Secretion in Epithelial Tissues: New Methodology Estimating Activity of Electro-Neutral Cl(-) Transporter.Frontiers in physiology · 2015Article
- Functional consequences of NKCC2 splice isoforms: insights from a Xenopus oocyte model.American journal of physiology. Renal physiology · 2014Article
- Fluid dilution and efficiency of Na(+) transport in a mathematical model of a thick ascending limb cell.American journal of physiology. Renal physiology · 2013Article
- Kinetics of hyperosmotically stimulated Na-K-2Cl cotransporter in Xenopus laevis oocytes.American journal of physiology. Cell physiology · 2011Article
- A tool for multi-scale modelling of the renal nephron.Interface focus · 2011Article
- Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule.American journal of physiology. Cell physiology · 2011Article
- A mathematical model of rat ascending Henle limb. II. Epithelial function.American journal of physiology. Renal physiology · 2010Article
- A mathematical model of rat ascending Henle limb. III. Tubular function.American journal of physiology. Renal physiology · 2010Article
- A possible catalytic role for NH4+ in Na+ reabsorption across the thick ascending limb.American journal of physiology. Renal physiology · 2010Article
- Mathematical modeling of kidney transport.Wiley interdisciplinary reviews. Systems biology and medicineReview
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Abstract
Kinetic models of Na+-K+-2Cl- costransporter (NKCC2) and K+-Cl- cotransporter (KCC4), two of the key cotransporters of the Henle limb, are fashioned with inclusion of terms representing binding and transport of NH4+. The models are simplified using assumptions of equilibrium ion binding, binding symmetry, and identity of Cl- binding sites. Model parameters are selected to be consistent with flux data from expression of these transporters in oocytes, specifically inwardly directed coupled transport of rubidium. In the analysis of these models, it is found that despite the simplifying assumptions to reduce the number of model parameters, neither model is uniquely determined by the data. For NKCC or KCC there are two- or three-parameter families of "optimal" solutions. As a consequence, one may specify several carrier translocation rates and/or ion affinities before fitting the remaining coefficients to the data, with no loss of fidelity in simulating the experiments. Model calculations suggest that with respect to NKCC2 near its operating point, the curve of ion flux as a function of cell Cl- is steep, and with respect to KCC4, its curve of ion flux as a function of peritubular K+ is also steep. The implication is that the kinetics are suitable for these two transporters in series to act as a sensor for peritubular K+, to modulate AHL Na+ reabsorption, with cytosolic Cl- as the intermediate variable. The models also reveal the potential for luminal NH4+ to be a potent catalyst for NKCC2 Na+ reabsorption, provided suitable exit mechanisms for NH4+ (from cell-to-lumen) are operative. It is found that KCC4 is likely to augment the secretory NH4+ flux, with peritubular NH4+ uptake driven by the cell-to-blood K+ gradient.
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