Regulation of Cl-dependent K transport by oxy-deoxyhemoglobin transitions in trout red cells

Borgèse, Franck; Motais, R; Garcia-Romeu, F

doi:10.1016/0005-2736(91)90194-d

Cited by 77 publications

(64 citation statements)

References 21 publications

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“…This binding is sensitive to hemoglobin oxygenation (33). The data associated with our results, which suggest a role of tAE1 in regulating other transport functioning, might provide an explanation of oxygen control of the KCl cotransporter as well as the Na ϩ /H ϩ exchanger in trout erythrocyte (34,35). Indeed, the oxygen sensitivity of these two transporters could be mediated by tAE1 interacting with hemoglobin on one side and with these transporters on the other.…”

Section: Discussionsupporting

confidence: 58%

Evidence for Up-regulation of the Endogenous Na-K-2Cl Co-transporter by Molecular Interactions with the Anion Exchanger tAE1 Expressed in Xenopus Oocyte

Guizouarn

Gabillat

Borgèse

2004

Journal of Biological Chemistry

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Expression of trout anion exchanger 1 (tAE1) in Xenopus oocyte led to the stimulation of a Na ؉ -and Cl ؊ -dependent Rb influx. Functional features and pharmacological data strongly suggest that this Rb influx is mediated by the endogenous Na-K-2Cl (NKCC) co-transporter. The functional relationship between expression of tAE1 and activation of the NKCC co-transporter was investigated. Indeed, it was shown previously that tAE1 expressed in Xenopus oocyte induces a strong anion conductance which is correlated with an increased taurine permeability. Measurements of intracellular ion contents ruled out the involvement of any modification of known electrochemical parameters in NKCC co-transporter activation by tAE1. Furthermore, using chimera of tAE1 made with AE1 from other species unable to exhibit anion conductance led to the conclusion that there was no correlation between tAE1 anion conductance and NKCC co-transporter stimulation. Therefore, a possible molecular interaction between tAE1 and the NKCC co-transporter was investigated. Our results clearly show that NKCC activation is dependent upon the C-terminal part of tAE1. Chimeric constructions where tAE1 C-terminal part was substituted by the corresponding part of mouse AE1 abolished co-transporter activation. Moreover, steric encumbrance on the C-terminal end of tAE1 with a specific antibody or with a protein fusion also prevented the co-transporter activation. These data suggest a new role for some anion exchangers in controlling other transporter activity by molecular interactions.

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Section: Discussionsupporting

confidence: 58%

Evidence for Up-regulation of the Endogenous Na-K-2Cl Co-transporter by Molecular Interactions with the Anion Exchanger tAE1 Expressed in Xenopus Oocyte

Guizouarn

Gabillat

Borgèse

2004

Journal of Biological Chemistry

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“…Nevertheless, cells maintained in Nµ exhibited considerable volume sensitivity: the ratio of K¤ influx in swollen cells to that in shrunken cells was 1·83 ± 0·10 (n = 16) in Nµ and 2·35 ± 0·20 (n = 16) in Oµ. In other species (Canessa et al 1987;Borgese et al 1991;Nielsen et al 1992;Honess et al 1996), the volume-sensitive K¤ influx, mediated via the KCl cotransporter, is entirely Oµ dependent. The apparent difference in behaviour of LK sheep red cells was therefore investigated further.…”

Section: Resultsmentioning

confidence: 92%

Oxygen‐dependent K⁺ fluxes in sheep red cells

Campbell

Gibson

1998

The Journal of Physiology

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This study was designed to investigate the O2 dependence of K+ influx in sheep red cells. Influx was determined using 86Rb+ as a tracer for K+; glass tonometers coupled to a gas mixing pump were used to equilibrate cell samples to the requisite oxygen tension (PO2). Both volume‐ and H+‐stimulated K+ influxes in low potassium‐containing (LK) sheep red cells were approximately doubled on equilibration with O2 relative to influxes measured in N2. O2‐dependent influxes were abolished when Cl− was replaced with NO3−, consistent with mediation by the KCl cotransporter. At pH 7, PO2 required for half‐maximal stimulation was 56 ± 1 mmHg (mean ± s.e.m., 3 sheep) for the O2‐dependent component of K+ influx: thus PO2 values over the physiological range affected K+ influx. K+ influx in fully deoxygenated sheep red cells showed substantial volume and H+ sensitivity. These residual components in N2 were also Cl− dependent, indicating that the KCl cotransporter of LK sheep red cells was active in the absence of O2. Volume‐sensitive K+ influxes in high potassium‐containing (HK) sheep red cells responded in a similar way to those in cells from LK sheep, although much smaller in magnitude, showing that intracellular [K+] had no significant effect on the O2 dependence of the cotransporter. Intracellular [Mg2+] ([Mg2+]i) was altered by incubating sheep red cells with A23187 (20 μM) and different values of extracellular [Mg2+] ([Mg2+]o). Total [Mg2+]i was determined by atomic absorption spectroscopy and free [Mg2+]i from [Mg2+]o and the Donnan ratio. Total [Mg2+]i was 1.29 ± 0.08 mM (mean ± s.e.m., n= 5), similar to that reported in the literature. Estimates of free [Mg2+]i showed an increase from 0.39 ± 0.05 in oxygenated cells to 0.52 ± 0.04 mM (mean ± s.e.m., n= 5; P < 0.05) in deoxygenated ones. Finally, although K+ influxes were altered by pharmacological loading or depletion of cells with Mg2+, the free [Mg2+]i required to affect influxes significantly was outside the physiological range. Results are difficult to reconcile with PO2 modulating KCl cotransport activity directly via changes in free [Mg2+]i or [Mg2+‐ATP]i.

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“…[2][3][4][30][31][32][33][34] The question therefore arises whether the deoxyHb binding sequence on human band 3 might be conserved in these other species. Although amino acid insertions and deletions frequently occur near the NH 2 -termini of all band 3 homologs, a region of high homology can nevertheless be identified in mammalian and avian sequences 35 but not in the sequences of fish (rainbow trout and zebrafish) band 3 homologs (Figure 7).…”

Section: Homology Analysismentioning

confidence: 99%

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

104

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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Regulation of Cl-dependent K transport by oxy-deoxyhemoglobin transitions in trout red cells

Cited by 77 publications

References 21 publications

Evidence for Up-regulation of the Endogenous Na-K-2Cl Co-transporter by Molecular Interactions with the Anion Exchanger tAE1 Expressed in Xenopus Oocyte

Evidence for Up-regulation of the Endogenous Na-K-2Cl Co-transporter by Molecular Interactions with the Anion Exchanger tAE1 Expressed in Xenopus Oocyte

Oxygen‐dependent K⁺ fluxes in sheep red cells

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

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Regulation of Cl-dependent K transport by oxy-deoxyhemoglobin transitions in trout red cells

Cited by 77 publications

References 21 publications

Evidence for Up-regulation of the Endogenous Na-K-2Cl Co-transporter by Molecular Interactions with the Anion Exchanger tAE1 Expressed in Xenopus Oocyte

Evidence for Up-regulation of the Endogenous Na-K-2Cl Co-transporter by Molecular Interactions with the Anion Exchanger tAE1 Expressed in Xenopus Oocyte

Oxygen‐dependent K+ fluxes in sheep red cells

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

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Oxygen‐dependent K⁺ fluxes in sheep red cells