Parameter estimation for a mathematical model of a non-gastric H+(Na+)/K+(NH4+) ATPase.

Parameter estimation for a mathematical model of a non-gastric H+(Na+)/K+(NH4+) ATPase. Am J Physiol Renal Physiol. 2015 Jun 24;:ajprenal.00539.2014 Authors: Nadal-Quirós M, Moore LC, Marcano M Abstract The role of the non-gastric H(+)/K(+) ATPase (HKA) in ion homeostasis of macula densa (MD) cells is an open question. To begin to explore this issue, we developed two mathematical models that describe the ion fluxes through a non-gastric HKA. One model assumes a 1H(+):1K(+)-per-ATP stoichiometry; the other assumes a 2H(+):2K(+)-per-ATP stoichiometry. Both models include Na(+) and NH4 (+) competitive binding with H(+) and K(+), respectively, a characteristic observed in vitro and in situ. Model rate constants were obtained by minimizing the distance between model and experimental outcomes. Both models, 1H(+)(1Na(+)):1K(+)(1NH4 (+))-per-ATP and 2H(+)(2Na(+)):2K(+)(2NH4 (+))-per-ATP, fit well the experimental data. Using both models, we simulated the ion net fluxes as a function of cytosolic or luminal ion concentrations typical for the cortical thick ascending limb and MD region. We observed that: K(+) and NH4 (+) flowed in the lumen-to-cytosol direction; there was competitive behavior between luminal K(+) and NH4 (+) and between cytosolic Na(+) and H(+); ion fluxes were highly sensitive to changes in cytosolic [Na(+)] or [H(+)]; the transporter does mostly Na(+)/K(+) exchange under physiological conditions. These results support the c...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research