Abstract
The Na+/H+ exchanger (NHE) plays a central role in regulating the intracellular pH in cardiac myocytes. We have developed a kinetic model of NHE which could put together major experimental findings. The ion transporting was described as 6-state and 8-state model to embody the process of ion binding and transitions. Proton-regulatory site was also considered with both intracellular and extracellular H+ binding sites. The activation by intracellular H+ was expressed with a Hill equation with various coefficients, and the effect of extracellular H+ was presumed inhibitory. Then, a Levenberg-Marquardt fitting method was applied to the experimental data. Plenty of minima of chi-square function were sought out using numerous starting points. Subsequently, the parameter sets were selected which satisfied the established properties of NHE. Comparison of the least chi-square revealed that the 8-state model with the activation Hill coefficient 3 gave better fitting results. To examine the validity of the model, it was implemented to a simple cell model which was composed of intrinsic pH buffer, Na+/K+ pump, NH3/NH4+ flux and others. When the change of intracellular pH was well reproduced during an acid load, the accompanying change of [Na+]i was compatibly simulated. In conclusion, our new NHE model is applicable to further investigation into the pH homeostasis under physiological and pathophysiological conditions. [J Physiol Sci. 2008;58 Suppl:S210]
