A quantitative description of the Na,K,2Cl cotransporter and ts conformity with experimental data

In epithelia, the Na,K,2Cl co-transporter acts in concert with other transport mechanisms to produce transepithelial NaCl transport. The reaction cycle for the Na,K,2Cl co-transporter has been well established experimentally, but whether it accounts, quantitatively, for the experimental findings has yet to be established. The differential equations that describe the reaction cycle were formulated and steady-state solutions obtained by digital computation. Conformity between this description and experimental data obtained from the literature was explored by automated searches for the sets of rate constants that yielded statistical best-fits to the experimental data. Fits were obtained to data from renal epithelia, fish intestinal epithelia, and human and duck erythrocytes. For example, in membrane vesicles prepared from isolated cells of the thick ascending limb of Henle activation curves for sodium uptake vs. extracellular K⁺, Na⁺, and Cl^- were fit. Results from this experiment provide important information concerning the mechanism of Na,K,2Cl co-transport and its potential role in epithelial ion transport. iN.C. Heart Grant NC95GS20).