Oxygen sensitivity of red cell membrane transporters revisited

Drew, C.; Ball, Vicky; Robinson, Hannah; Ellory, J. Clive; Gibson, John S.

doi:10.1016/j.bioelechem.2003.07.003

Cited by 28 publications

(40 citation statements)

References 30 publications

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“…Because this conformational communication is also abrogated by band 3 labeling with DIDS, a related signal transduction pathway can be envisioned to account for oxygenation effects on Na ϩ /K ϩ transport. 4,8,10 Because much remains to be learned about mechanisms of communication between band 3 and associated proteins, it will be important to test the above hypotheses in transgenic mice in which deoxyHb binding to band 3 has been either eliminated or enhanced by introduction of the appropriate mutations.…”

Section: Discussionmentioning

confidence: 99%

“…First, the activities of many membrane solute transporters change with the oxygen content of the cell, including volume regulatory transporters (eg, Na ϩ /H ϩ exchanger), cation coupled Cl Ϫ cotransporters, amino acid transporters, and ion channels. [1][2][3][4][5][6][7][8][9][10] The K/Cl cotransporter, for example, is reported to be 20-fold more active in oxygenated than in deoxygenated RBCs. 9,10 Second, erythrocyte metabolism is modulated by the O 2 tension of the medium.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10] The K/Cl cotransporter, for example, is reported to be 20-fold more active in oxygenated than in deoxygenated RBCs. 9,10 Second, erythrocyte metabolism is modulated by the O 2 tension of the medium. Thus, glucose flux through the pentose phosphate pathway proceeds twice as rapidly in oxygenated as in deoxygenated cells, and glucose consumption in glycolysis is inhibited by oxygenation.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the deoxyhemoglobin binding site on human erythrocyte band 3: implications for O2 regulation of erythrocyte properties

Chu

Breite

Ciraolo

et al. 2008

Blood

109

131

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Band 3, the major protein of the human erythrocyte membrane, associates with multiple metabolic, ion transport, and structural proteins. Functional studies demonstrate that the oxygenation state of the erythrocyte regulates cellular properties performed by these and/or related proteins. Because deoxyhemoglobin, but not oxyhemoglobin, binds band 3 reversibly with high affinity, these observations raise the hypothesis that hemoglobin might regulate erythrocyte properties through its reversible, oxygenationdependent association with band 3. To explore this hypothesis, we have characterized the binding site of deoxyHb on human erythrocyte band 3. We report that (1) deoxyHb binds to residues 12-23 of band 3; (2) mutation of residues on either side of this sequence greatly enhances affinity of deoxyHb for band 3, suggesting that evolution of a higher affinity interaction would have been possible had it been beneficial for survival; (3) Hb does not bind to 2 other sequences in band 3 despite their high sequence homology to residues 12-23, and (4) IntroductionSeveral lines of evidence suggest that the oxygenation state of the erythrocyte (RBC) regulates multiple erythrocyte properties. First, the activities of many membrane solute transporters change with the oxygen content of the cell, including volume regulatory transporters (eg, Na ϩ /H ϩ exchanger), cation coupled Cl Ϫ cotransporters, amino acid transporters, and ion channels. [1][2][3][4][5][6][7][8][9][10] The K/Cl cotransporter, for example, is reported to be 20-fold more active in oxygenated than in deoxygenated RBCs. 9,10 Second, erythrocyte metabolism is modulated by the O 2 tension of the medium. Thus, glucose flux through the pentose phosphate pathway proceeds twice as rapidly in oxygenated as in deoxygenated cells, and glucose consumption in glycolysis is inhibited by oxygenation. 11 Third, erythrocyte deoxygenation may affect membrane structural properties. For example, deoxygenated hemoglobin (Hb) (but not oxygenated Hb [oxyHb]) competes with ankyrin for binding to band 3, and band 3 retention in detergent-extracted membrane skeletons is greatly reduced in skeletal pellets from deoxygenated cells (M. Stefanovic and P.S.L., unpublished data, December 2005). Furthermore, ankyrin epitopes are more accessible to antiankyrin antibodies in deoxygenated than in oxygenated RBCs. Taken together, these latter findings imply a looser association of ankyrin with the membrane in deoxygenated than in oxygenated erythrocytes.In searching for a mechanism to account for oxygenation effects on red cell properties, identification of both the O 2 sensor and downstream effector was considered important. A major candidate for the O 2 sensor was presumed to be Hb, because the O 2 dependence of the above properties generally follows the O 2 dissociation curve of Hb. 4,12,13 The downstream effector has been more uncertain, but band 3 has represented the prime candidate, because it constitutes the only established binding site of Hb on the membrane. Moreover, multiple observation...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of the deoxyhemoglobin binding site on human erythrocyte band 3: implications for O2 regulation of erythrocyte properties

Chu

Breite

Ciraolo

et al. 2008

Blood

109

131

View full text Add to dashboard Cite

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“…This also applies to the transporters involved in volume regulation (Jensen, 1995;Nielsen, 1997;Gibson et al, 2000;Brauner et al, 2002;Drew et al, 2004). In Bufo marinus, there is a strong P O 2 dependency of the shrinkage-induced Na influx, with maximal stimulation at low P O 2 during the initial 30·min (Fig.·1).…”

Section: Discussionmentioning

confidence: 93%

“…In addition to shrinkage, the activity of the NHE and NKCC and other RBC ion transporters is modulated by oxygen, catecholamines or acidification [NHE (Motais et al, 1987;Salama and Nikinmaa, 1988;Nielsen, 1997;Virkki et al, 1998) and NKCC Muzyamba et al, 1999;Flatman, 2005;Berenbrink et al, 2006)]. Thus, in various vertebrates, the NHE, NKCC and/or RVI response are inhibited in airequilibrated cells compared with cells at low oxygen partial pressure (P O 2) (Gibson et al, 2000;Brauner et al, 2002;Jensen et al, 2002;Drew et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Oxygen-sensitive regulatory volume increase and Na transport in red blood cells from the cane toad,Bufo marinus

Kristensen

Koldkjær

Berenbrink

et al. 2007

Journal of Experimental Biology

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SUMMARY The red blood cells (RBCs) of cane toad, Bufo marinus, are only partially saturated with oxygen in most of the circulation due to cardiac shunts that cause desaturation of arterial blood. The present study examines the oxygen dependency of RBC ouabain-insensitive unidirectional Na transport,using 22Na, in control cells and in cells exposed to hyperosmotic shrinkage or the β-adrenergic agonist isoproterenol. Deoxygenation per se induced a slow, but significant Na influx, which was paralleled by a slow increase in RBC volume. Hyperosmotic shrinkage by a calculated 25% activated a robust Na influx that in the first 30 min had a strong PO2 dependency with maximal activation at low PO2 values and a P50of ∼5.5 kPa. This activation was completely abolished by the Na/H exchanger (NHE) inhibitor EIPA (10–4 mol l-1). Hyperosmotic shrinkage is particularly interesting in B. marinus as it withstands considerable elevation in extracellular osmolarity following dehydration. Parallel studies showed that deoxygenated B. marinusRBCs had a much faster regulatory volume increase (RVI) response than air-equilibrated RBCs, reflecting the difference in magnitude of Na influxes at the two PO2 values. The extent of RVI(∼60%) after 90 min, however, was similar under the two conditions,reflecting a more prolonged elevation of the shrinkage-induced Na influx in air-equilibrated RBCs. There were no significant differences in the ability to perform RVI between whole blood cells at a PCO2of 1 and 3 kPa or washed RBCs, and 10–4 mol l-1amiloride reduced the RVI under all conditions, whereas 10–5mol l-1 bumetanide had no effect. Isoproterenol(10–5 mol l-1) induced a significant and prolonged increase in an EIPA-sensitive and bumetanide-insensitive Na influx at low PO2 under iso-osmotic conditions, whilst there was no stimulation by isoproterenol for up to 45 min in air-equilibrated RBCs. The prolonged β-adrenergic activation of the Na influx at low PO2 is distinctly different from the rapid and transient stimulation in teleost RBCs, suggesting significant differences in the signal transduction pathways leading to transporter activation between vertebrate groups.

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