title: Direct inhibition of phospholipid scrambling activity in erythrocytes by potassium ions.
abstract: The exposure of phosphatidylserine (PS) at the cell surface plays a critical role in blood coagulation and serves as a macrophage recognition moiety for the engulfment of apoptotic cells. Previous observations have shown that a high extracellular [K(+)] and selective K(+) channel blockers inhibit PS exposure in platelets and erythrocytes. Here we show that the rate of PS exposure in erythrocytes decreases by approximately 50% when the intracellular [K(+)] increases from 0 to physiological concentrations. Using resealed erythrocyte membranes, we further show that lipid scrambling is inducible by raising the intracellular [Ca(2+)] and that K(+) ions have a direct inhibitory effect on this process. Lipid scrambling in resealed ghosts occurs in the absence of cell shrinkage and microvesicle formation, processes that are generally attributed to Ca(2+)-induced lipid scrambling in intact erythrocytes. Thus, opening of Ca(2+)-sensitive K(+) channels causes loss of intracellular K(+) that results in reduced intrinsic inhibitory effect of these ions on scramblase activity.
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: J L N
authors.initials: JL
authors.lastname: Wolfs
authors.forename: P
authors.initials: P
authors.lastname: Comfurius
authors.forename: O
authors.initials: O
authors.lastname: Bekers
authors.forename: R F A
authors.initials: RF
authors.lastname: Zwaal
authors.forename: K
authors.initials: K
authors.lastname: Balasubramanian
authors.forename: A J
authors.initials: AJ
authors.lastname: Schroit
authors.forename: T
authors.initials: T
authors.lastname: Lindhout
authors.forename: E M
authors.initials: EM
authors.lastname: Bevers
mesh_terms: D002118:Calcium / Q000378:metabolism; D048430:Cell Shape; D004910:Erythrocyte Membrane / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007477:Ions / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D007476:Ionophores; D007477:Ions; D008563:Membrane Lipids; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D015759:Ionomycin; D013925:Thromboplastin; D012964:Sodium; D011188:Potassium; D002118:Calcium