1. The K+/Cl− co-transport system is activated by a number of interventions, such as cell swelling and stimulation with N-ethylmaleimide. It is specifically inhibited by R(+)-[(dihydroindenyl)oxy]alkanoic acid and requires the presence of K+ and Cl− on the same side of the cell membrane. This co-transporter has been studied extensively, mainly in erythrocytes of many species, in which it plays a key role in cell volume regulation. Here we present evidence that human platelets contain K+/Cl− co-transporters.
2. We have studied the efflux of 86Rb+ (a marker for K+) from 86Rb+-loaded human platelets, and have defined their response to stimulation by N-ethylmaleimide.
3. N-Ethylmaleimide (0.5 and 1 mmol/l) stimulated an increase in cumulative 86Rb+ efflux in a concentration-dependent manner. This efflux was inhibited by R(+)-[(dihydroindenyl)oxy]alkanoic acid (10 μmol/l) but was insensitive to bumetanide. It also required the presence of external Cl−.
4. These observations suggest that 86Rb+ efflux from the platelets stimulated by N-ethylmaleimide occurs via K+/Cl− co-transport.
5. When the K+/Cl− co-transporter was stimulated by N-ethylmaleimide we were unable to stimulate the Na+/K+/2Cl− co-transporter with a high external concentration of KCl or inhibit 86Rb+ efflux with bumetanide. Together with other evidence, this suggests that when the K+/Cl− co-transporter is stimulated with N-ethylmaleimide, the Na+/K+/2Cl− co-transporter is inhibited.