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Estimation of Acid‐Base and NH + 4 Transport Parameters in a TAL Cell Model Using Inverse Methods
Author(s) -
NievesGonzalez Aniel,
Marcano Mariano,
Clausen Chris,
Layton Harold E.,
Moore Leon C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.602.21
Subject(s) - chemistry , cytosol , cotransporter , biophysics , paracellular transport , inverse , membrane , biochemistry , mathematics , sodium , geometry , biology , organic chemistry , permeability (electromagnetism) , enzyme
A mathematical model of a medullary thick ascending limb (mTAL) cell was used to study cytosolic pH (pH i ) responses to luminal NH 4 + perturbations. TAL cells load NH 4 + via apical NH 4 + ‐permeable channels and the NKCC2 cotransporter, resulting in a rapid fall in pH i . Our goal was to use our model and published NH 4 + perturbation data to estimate parameters associated with pH i regulation using an inverse method. The TAL cell model, which includes NH + 4 binding by NKCC2 and NHE, also includes models for Na + ,K + ‐ATPase, the Cl−‐HCO 3− exchanger, KCC1, and trans‐ and paracellular electrodiffusion. A least‐squares problem was formulated and solved to fit the model to the data. First, steady‐state short‐circuit current data was used to estimate parameters important in Na + transport; this yielded reasonable cytosolic concentrations, membrane PD's and resistances. The model was then fit to time records of NH 4 + perturbations, with and without inhibition of NKCC2 or K + channels, to estimate parameters associated with NH 4 + transport. The results show that our TAL cell model, when used with parameter sets obtained from optimization methods, exhibits behaviors consistent with a wide variety of experimental results, including NH 4 + perturbations, in isolated perfused TAL segments. This provides validation of the TAL model, which we intend to use in a multi‐cell model of the TAL segment.