Abnormal regulation of Mg2+ transport via Na/Mg exchanger in sickle erythrocytes

Blood. 2005 Jan 1;105(1):382-6. doi: 10.1182/blood-2003-11-3755. Epub 2004 Sep 7.

Abstract

Erythrocyte magnesium (Mg2+) deficiency has been demonstrated in sickle cell disease to contribute to erythrocyte dehydration, K loss, and thus sickling. No studies have assessed the functional properties of the Na/Mg exchanger in sickle cell disease. Using Mg(2+)-loaded erythrocytes, we measured Mg2+ efflux induced by extracellular Na+. We estimated that the Na/Mg exchanger had higher maximal velocity, higher affinity for Na+, and lower cooperativity for Mg2+ in sickle than in normal erythrocytes. The activity of the exchanger was markedly decreased by hypotonic and hypertonic conditions in normal erythrocytes but not in sickle erythrocytes. Studies of density-separated erythrocytes showed that the activity of the exchanger decreased as the mean cellular hemoglobin concentration increased in normal but not in sickle erythrocytes. Inhibition of protein kinase C (PKC) activity by calphostin C and chelerythrine increased the activity of the exchanger in normal but not in sickle erythrocytes. Inhibition of serine/threonine phosphatases did not affect the activity of the exchanger in either normal or sickle erythrocytes. Altogether, these data indicate that the Na/Mg exchanger is abnormally regulated in sickle erythrocytes. Therefore, Mg2+ depletion in sickle erythrocytes might be mediated by an up-regulated Na/Mg exchanger, possibly by dephosphorylation of the transporter or a closely associated regulator.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / metabolism*
  • Anemia, Sickle Cell / pathology*
  • Antiporters / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Erythrocytes / metabolism*
  • Erythrocytes / pathology
  • Humans
  • Ion Transport
  • Kinetics
  • Magnesium / metabolism*
  • Osmolar Concentration
  • Phosphoric Monoester Hydrolases / antagonists & inhibitors
  • Phosphoric Monoester Hydrolases / metabolism
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Sodium / metabolism

Substances

  • Antiporters
  • Enzyme Inhibitors
  • sodium-magnesium antiporter
  • Sodium
  • Protein Kinase C
  • Phosphoric Monoester Hydrolases
  • Magnesium