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Estimation of NKCC2 Transporter Model Parameters from Binding Kinetics
Author(s) -
Marcano Mariano,
Yang HunMo,
Clausen Chris,
Moore Leon C
Publication year - 2006
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.20.5.a1223-d
Subject(s) - estimation , transporter , kinetics , econometrics , statistics , chemistry , mathematics , economics , biochemistry , physics , gene , quantum mechanics , management
Our goal was to determine if parameters for a thermodynamically consistent kinetic (TCK) model of the NKCC2 transporter can be identified from 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, the NKCC2 model is a system of linear equations with 8 unknown parameters. We used the following procedure to identify TCK model parameters for the A, B, and F isoforms of the NKCC2 transporter from published binding kinetic data (Plata, et al, JBC 277:11004, 202): 1) the Hill equation was used to estimate Vmax, and the data rescaled into standard units with consistent Vmax; 2) a nonlinear least‐squares optimization method was used to estimate the unknown parameters. The resulting models all predict curves consistent with the binding data, and all exhibit proper behavior at very low ion concentrations. However, because of parameter co‐dependencies and typical experimental noise, the parameter sets are not unique, but all sets produce essentially identical curves, as do models with 7 or 6 parameters simplified to reduce co‐dependencies. Hence, this approach provides a systematic means to obtain TCK models of cotransport which are sufficient for use in models of epithelial cells. Funded by NIH grant S06GM08102.