Cell shrinkage activates Na+/H+ exchange in dog red cells by relieving inhibition of exchange by Na+ in isotonic medium.

Na+/H+ exchangers (NHE) are widely distributed transporters responsible for regulation of cell volume and pH. In isotonic medium, NHE is often low or negligible, and is strongly activated by osmotic cell shrinkage. It is reported here that extracellular Na+ inhibits NHE in isotonic medium, and cell shrinkage stimulates NHE by relieving this inhibition. There is more than one inhibitory Na+ site on each transporter. Shrinkage activates NHE by decreasing the apparent affinity for Na+ at the inhibitory sites. Shrinkage has no effect on the apparent affinity for Na+ at the substrate sites for activation of NHE.