Regulatory volume increase in Ehrlich ascites tumor cells.

Ehrlich ascites tumor cells, shrunken as a result of KCl-depletion and Na+ loading, re-establish normal ionic concentrations by the combined activity of the Na+/K+ pump and the (2Cl- + K+ + Na+) cotransport system. Restoration of cell volume, however, correlates only with the increase in intracellular Cl-. This along with the finding that the equilibrium volume is linearly related to the steady state [Cl-] suggests that the extent to which cell volume increases is determined by Cl- transport. Net Cl- uptake, which is mediated almost exclusively by the cotransport system, is ultimately responsible for establishing the steady-state intracellular Cl- concentration. Transport mediated by this pathway ceases when the sum of the chemical potentials for Na+, K+ and Cl- approaches zero and corresponds with the establishment of a steady state for Cl-. These findings suggest that Cl- plays a key role in the regulation of net cotransport activity and thereby cell volume.