title: Na+/H+ exchange is increased in sickle cell anemia and young normal red cells.
abstract: Red cell volume regulation is important in sickle cell anemia because the rate and extent of HbS polymerization are strongly dependent on initial hemoglobin concentration. We have demonstrated that volume-sensitive K:Cl cotransport is highly active in SS whole blood and is capable of increasing MCHC. We now report that Na+/H+ exchange (Na/H EXC), which is capable of decreasing the MCHC of erythrocytes with pHi less than 7.2, is also very active in the blood of patients homozygous for HbS. The activity of Na/H EXC (maximum rate) was determined by measuring net Na+ influx (mmol/liter cell.hr = FU) driven by an outward H+ gradient in oxygenated, acid-loaded (pHi6.0), DIDS-treated SS cells. The Na/H EXC activity was 33 +/- 3 FU (mean +/- SE) (n = 19) in AA whites, 37 +/- 8 FU (n = 8) in AA blacks, and 85 +/- 15 FU (n = 14) in SS patients (P less than 0.005). Separation of SS cells into four density-defined fractions by density gradient revealed mean values of Na/H EXC four to five times higher in reticulocytes (SS1), discocytes (SS2) and dense discocytes (SS3), than in the fraction containing irreversibly sickled cells and dense discocytes (SS4). In contrast to K:Cl cotransport, which dramatically decreases after reticulocyte maturation, Na/H EXC persists well after reticulocyte maturation. In density-defined, normal AA red cells, Na/H EXC decreased monotonically as cell density increased. In SS and AA red cells, the magnitude of stimulation of Na/H EXC by cell shrinkage varied from individual to individual.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Endocrine-Hypertension Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: M
authors.initials: M
authors.lastname: Canessa
authors.forename: M E
authors.initials: ME
authors.lastname: Fabry
authors.forename: S M
authors.initials: SM
authors.lastname: Suzuka
authors.forename: K
authors.initials: K
authors.lastname: Morgan
authors.forename: R L
authors.initials: RL
authors.lastname: Nagel
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D004905:Erythrocyte Aging; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000378:metabolism*; D006441:Hemoglobin A; D006451:Hemoglobin, Sickle; D006801:Humans; D007474:Ion Exchange; D007700:Kinetics; D011522:Protons; D012156:Reticulocytes / Q000378:metabolism; D012964:Sodium / Q000097:blood*; D017923:Sodium-Hydrogen Exchangers
chemical_list: D002352:Carrier Proteins; D006451:Hemoglobin, Sickle; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; C028672:hemoglobin AA; D006441:Hemoglobin A; D012964:Sodium