| dc.description | An optimization algorithm was used to compute parameter values for kinetic models of NH+4 transport by the renal Na-K-2Cl cotransporter (NKCC2) and K-Cl cotransporter (KCC). The
optimization method finds model off-binding and translocation rate constants by minimizing the
difference between model unidirectional fluxes and published data on NH+
4
-dependent 86Rb+
uptake by the NKCC and KCC transporters in transfected Xenopus oocytes. The computed
parameters for each model yielded fluxes consistent with the experimental curves. However, a
systematic exploration of the parameter space revealed that, in some models, different parameter
sets yield essentially identical fits to the data. With the identified parameters, the NKCC models
show K+/NH+
4
exchange and enhancement of Na+ uptake by NH+
4
binding when external K+
concentration is low. Further, under these conditions, substantial rates of K+/NH+
4
exchange are
predicted, which may prevent depletion of luminal K+. For the KCC models, in the medulla
where the interstitial concentration of ammonium is high, substantial rates of K+/NH+
4
exchange
are again predicted to occur. | |
