OKADAIC ACID INHIBITS ACTIVATION OF K-CL COTRANSPORT IN RED-BLOOD-CELLS CONTAINING HEMOGLOBIN-S AND HEMOGLOBIN-C

The sensitivity of red blood cells containing hemoglobins S and C to activation of K-Cl cotransport by osmotic swelling and acidification was reduced by okadaic acid, a specific protein phosphatase inhibitor. The dose-response curve for okadaic acid suggests its action is on a type 1 protein phosphatase. Okadaic acid has been previously shown to inhibit swelling-induced activation of K-Cl cotransport in red blood cells from rabbits, normal humans, and dogs. The present work confirms the observation that okadaic acid blunts the stimulation of K-Cl cotransport by cell swelling. The new information is that okadaic acid reduces the effects of hemoglobins S and C on the volume and pH sensitivity of K-Cl cotransport. Thus the influences of cell volume, pH, and mutant hemoglobins may all be mediated via a common mechanism that affects the phosphorylation state, either of the K-Cl cotransporter itself or of a protein that regulates its function.