Kinetic Models for Ammonium Transport by the NKCC2 Cotransporter

• Published in: The FASEB journal 2007, Vol.21 (6), p.A828-A828
• Main Authors: Marcano, Mariano, Yang, Hun‐Mo, Nieves‐González, Aniel, Clausen, Chris, Moore, Leon C
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.6.A828

A nonlinear least‐squares technique was applied to thermodynamically consistent kinetic (TCK) models for transport of ammonium by the NKCC2A cotransporter to identify model parameters that display typical ion binding kinetic curves. TCK models are needed to evaluate NKCC2 function when outside ion concentrations are sufficiently low to limit or reverse transport. Assuming equilibrium binding and asymmetry of the off‐binding and translocation rate constants, the model consists of a system of 15 linear equations with 11 unknown parameters. One can reduce the number of unknown parameters by assuming symmetry of some parameters. Models with 7 to 11 parameters were considered. For each model the least‐squares method was applied to identify parameter values which lead to kinetic curves in agreement with published binding kinetic data (Bergeron, et al, AJP 285: –F78, 2003 and Plata, et al, JBC 277:–11012, 2002). The models all predicted curves consistent with the binding data, and all exhibited proper behavior at very low ion concentrations. However, the model with highest binding symmetry showed smallest error and, thus, may be optimal. This approach provides a systematic means to obtain TCK models of cotransporters for use in models of epithelial cells. This research was supported by NIH grants S06GM08102 and DK‐042091