EVIDENCE FOR AN R(-[(DIHYDROINDENYL)OXY]ALKANOIC ACID-SENSITIVE K+())CL- COTRANSPORTER IN HUMAN PLATELETS AND ITS INTERACTION WITH THE NA+/K+/2CL-CO-TRANSPORTER/

1. The K+/Cl- co-transport system is activated by a number of interven tions, 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 m embrane. This co-transporter has been studied extensively, mainly in e rythrocytes of many species, in which it plays a key role in cell volu me regulation, Here we present evidence that human platelets contain K +/Cl- co-transporters. 2. We have studied the efflux of Rb-86(+) (a ma rker for K+) from Rb-86(+)-loaded human platelets, and have defined th eir response to stimulation by N-ethylmaleimide. 3. N-Ethylmaleimide ( 0.5 and 1 mmol/l) stimulated an increase in cumulative Rb-86(+) efflux in a concentration-dependent manner, This efflux was inhibited by R()-[(dihydroindenyl)oxy]alkanoic acid (10 mu mol/l) but was insensitive to bumetanide. It also required the presence of external Cl-. 4. Thes e observations suggest that Rb-86(+) efflux from the platelets stimula ted 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 con centration of KCI or inhibit Rb-86(+) efflux with bumetanide. Together with other evidence, this suggests that when the K+/Cl- co-transporte r is stimulated with N-ethylmaleimide, the Na+/K+/2Cl(-) co-transporte r is inhibited.