Parameter Estimation for Models of NH+ 4 Transport by the Renal Na-K-2Cl and K-Cl Cotransporters

Abstract

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.