Sodium-dependent ion cotransport in steady-state Ehrlich ascites tumor cells

The Ehrlich tumor cell possesses an anion-cation cotransport system which operates as a bidirectional exchanger during the physiological steady state. This cotransport system, like that associated with the volume regulatory mechanism (i.e. coupled net uptake of Cl- + Na+ and/or K+), is Cl- -selective and furosemide-sensitive, suggesting the same mechanism operating in two different modes. Since Na+ has an important function in the volume regulatory response, its role in steady-state cotransport was investigated. In the absence of Na+, ouabain-insensitive K+ and DIDS-insensitive Cl- transport (KCl cotransport) are low and equivalent to that found in 150 mM Na+ medium containing furosemide. Increasing the [Na+] results in parallel increases in K+ and Cl- transport. The maximum rate of each (18 to 20 meq/(kg dry wt) . min) is reached at about 20 mM Na+ and is maintained up to 55 mM. Thus, over the range 1 to 55 mM Na+ the stoichiometry of KCl cotransport is 1:1. In contrast to K+ and Cl-, furosemide-sensitive Na+ transport is undetectable until the [Na+] exceeds 50 mM. From 50 to 150 mM Na+, it progressively rises to 7 meq/(kg dry wt) . min, while K+ and Cl- transport decrease to 9 and 16 meq/(kg dry wt) . min, respectively. Thus, at 150 mM Na+ the stoichiometric relationship between Cl-, Na+ and K+ is 2:1:1. These results are consistent with the proposal that the Cl- -dependent cation cotransport system when operating during the steady state mediates the exchange of KCl for KCl or NaCl for NaCl; the relative proportion of each determined by the extracellular [Na+].