title: A mathematical model of rat distal convoluted tubule. I. Cotransporter function in early DCT.
abstract: A model of rat early distal convoluted tubule (DCT) is developed in conjunction with a kinetic representation of the thiazide-sensitive NaCl cotransporter (TSC). Realistic constraints on cell membrane electrical conductance require that most of the peritubular Cl(-) reabsorption proceeds via a KCl cotransporter,along with most of the K(+) recycled from the Na-K-ATPase. The model tubule reproduces the saturable Cl(-) reabsorption of DCT but not the micropuncture finding of linear Na(+) flux in response to load, more likely a feature of late DCT (CNT). As in proximal tubule, early DCT HCO(3)(-) reabsorption is mediated by a luminal Na(+)/H(+) exchanger (NHE), but in contrast to proximal tubule, the DCT exchanger is operating closer to equilibrium. In the model DCT, two consequences of the lesser driving force for NHE exchange are an acidic cytosol and wider swings in NHE flux with perturbations of luminal composition. Variations in luminal NaCl provide a challenge to cell volume, which can be blunted by volume dependence of the KCl cotransporter. Cell swelling can also be induced by increases in peritubular K(+) concentration. In this case, volume-dependent inhibition of TSC could provide volume homeostasis that also enhances distal Na(+) delivery, and ultimately enhances renal K(+) excretion. In the model DCT, proton secretion is blunted by peritubular HCO(3)(-), so that there is little contribution by this segment to the maintenance of metabolic alkalosis. During alkalosis, the model predicts that increasing luminal NaCl concentration enhances NHE flux, so that these calculations provide no support for a role of early DCT in recovery from Cl(-) depletion alkalosis.
authors.affiliation: Dept. of Physiology and Biophysics, Weill Medical College of Cornell Univ., 1300 York Ave., New York, NY 10021, USA. alan@nephron.med.cornell.edu
authors.forename: Alan M
authors.initials: AM
authors.lastname: Weinstein
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology; D000465:Algorithms; D000471:Alkalosis / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002463:Cell Membrane Permeability; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D004847:Epithelial Cells / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007674:Kidney Diseases / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D015233:Models, Statistical; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D049994:Sodium Potassium Chloride Symporter Inhibitors; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D001639:Bicarbonates; D049994:Sodium Potassium Chloride Symporter Inhibitors; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D006852:Hydrochlorothiazide; D012964:Sodium