SULFHYDRYL OXIDATION AND ACTIVATION OF RED-CELL K-CL- COTRANSPORT IN THE TRANSGENIC SAD MOUSE()

The SAD mouse is characterized by the expression of human SAD hemoglob in (Hb), a super S Hb with a higher tendency to polymerize than HbS du e to the presence of two additional mutations, Antilles beta 23(Ile) a nd D Punjab beta 121(Glu). Monovalent cation transport was studied in erythrocytes from SAD-1 (Hb SAD = 19%) and beta-thal/SAD-1 (Hb SAD = 2 6%) mice. Erythrocytes containing Hb SAD exhibited dehydration, increa sed maximal rate of Na+-K+ pump, unchanged Rb+ flux via the Gardos cha nnel, and increased K+-Cl- cotransport. K+-Cl- cotransport was defined as Cl--dependent (substitution with sulfamate or methanesulfonate) ok adaic acid-sensitive K+ efflux. Volume regulatory decrease via K+-Cl- cotransport was also increased in swollen SAD erythrocytes compared wi th controls. K+-Cl- cotransport was stimulated by staurosporine in all mouse strains, but the extent of stimulation was reduced in beta-thal /SAD-1 mice. Treatment with dithiothreitol reduced K+-Cl- cotransport activity in SAD-1 and beta-thal/SAD-1 mice to levels similar to that o f control strains, indicating that reversible sulfhydryl oxidation con tributes to the activated state of K+-Cl- cotransport in mouse erythro cytes that express transgenic human Hb SAD.