Document Detail

Modeling proximal tubule cell homeostasis: tracking changes in luminal flow.
MedLine Citation:
PMID:  19280266     Owner:  NLM     Status:  MEDLINE    
During normal kidney function, there are routinely wide swings in proximal tubule fluid flow and proportional changes in Na(+) reabsorption across tubule epithelial cells. This "glomerulotubular balance" occurs in the absence of any substantial change in cell volume, and is thus a challenge to coordinate luminal membrane solute entry with peritubular membrane solute exit. In this work, linear optimal control theory is applied to generate a configuration of regulated transporters that could achieve this result. A previously developed model of rat proximal tubule epithelium is linearized about a physiologic reference condition; the approximate linear system is recast as a dynamical system; and a Riccati equation is solved to yield the optimal linear feedback that stabilizes Na(+) flux, cell volume, and cell pH. The first observation is that optimal feedback control is largely consigned to three physiologic variables, cell volume, cell electrical potential, and lateral intercellular hydrostatic pressure. Parameter modulation by cell volume stabilizes cell volume; parameter modulation by electrical potential or interspace pressure act to stabilize Na(+) flux and cell pH. This feedback control is utilized in a tracking problem, in which reabsorptive Na(+) flux varies over a factor of two, in order to represent a substantial excursion of glomerulotubular balance. The resulting control parameters consist of two terms, an autonomous term and a feedback term, and both terms include transporters on both luminal and peritubular cell membranes. Overall, the increase in Na(+) flux is achieved with upregulation of luminal Na(+)/H(+) exchange and Na(+)-glucose cotransport, with increased peritubular Na(+)-3HCO(3)(-) and K(+)-Cl(-) cotransport, and with increased Na(+), K(+)-ATPase activity. The configuration of activated transporters emerges as a testable hypothesis of the molecular basis for glomerulotubular balance. It is suggested that the autonomous control component at each cell membrane could represent the cytoskeletal effects of luminal flow.
Alan M Weinstein; Eduardo D Sontag
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-03-12
Journal Detail:
Title:  Bulletin of mathematical biology     Volume:  71     ISSN:  1522-9602     ISO Abbreviation:  Bull. Math. Biol.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-13     Completed Date:  2009-09-28     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  0401404     Medline TA:  Bull Math Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1285-322     Citation Subset:  IM    
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MeSH Terms
Acid-Base Equilibrium / physiology
Biological Transport / physiology*
Cell Size
Epithelial Cells / physiology
Feedback, Physiological / physiology
Glucose / metabolism
Homeostasis / physiology*
Hydrogen-Ion Concentration
Hydrostatic Pressure
Ions / metabolism
Kidney Tubules, Proximal / cytology,  physiology*
Membrane Potentials / physiology
Models, Biological*
Urea / metabolism
Water-Electrolyte Balance / physiology
Grant Support
Reg. No./Substance:
0/Ions; 8W8T17847W/Urea; IY9XDZ35W2/Glucose

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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