Induction of a Ca2+-activated K+ channel in human erythrocytes by mechanical stress

Johnson, Robert M.; Tang, Ke

doi:10.1016/0005-2736(92)90418-l

Cited by 38 publications

(23 citation statements)

References 33 publications

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“…14,35 This provokes a transient dehydration and increased loss of intracellular potassium that is only partially offset by an increase in intracellular sodium. 14,34,36,37 If such a process takes place in the circulating LPC-treated RBCs, this would lead to a decrease in cell volume, creating a more favorable S/V ratio and enabling the surface-deficient RBCs to remain in the circulation. This hypothesis is supported by the fact that LPC-treated RBC dimensions were similar at T0 and T40 and both were significantly lower than that of untreated RBCs ( Figure 4A-C).…”

Section: Discussionmentioning

confidence: 99%

“…Third, the survival of an LPC-treated RBC subpopulation might be because of their S/V ratio returning toward normal values through a decrease in cell volume as a result of regulation of ions and water permeability of the cell. [2][3][4][5] It is well established that, when submitted to increased mechanical stress, normal RBCs exhibit a reversible increase in permeability to monovalent [2][3][4][5]32,33 and divalent 5,34 cations and to anions. 5 Such phenomena have been shown to be exacerbated when RBC membrane rigidity is increased 3 or when the surface area is reduced, as is the case in HS RBCs.…”

Section: Discussionmentioning

confidence: 99%

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Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen

Safeukui

Buffet

Deplaine

et al. 2012

Blood

118

139

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IntroductionDuring their 120-day life span, human RBCs repeatedly traverse capillaries of the vascular bed and interendothelial slits of the venous sinus of spleen red pulp, both of which are narrower than their smallest dimension. 1 This necessitates maintenance of the ability of RBCs to undergo repeated, extensive, and reversible deformations. Repeated major membrane deformations induce ion and water permeability changes in the RBCs. [2][3][4][5] The biconcave discoid shape endows the human RBC with an advantageous surface area-to-volume (S/V) ratio, allowing the cell to undergo marked deformations while maintaining a constant surface area. [6][7][8] A reduced RBC S/V ratio has long been recognized to contribute to pathogenesis of several RBC disorders, 9-11 including hereditary spherocytosis (HS), the most common cause of inherited chronic hemolytic anemia in Northern Europe and North America, with an estimated incidence of 1 in 2000. 11 The clinical presentation of HS can range from mild to severe hemolytic anemia. 12,13 The molecular basis of HS is heterogeneous, the common denominator being the loss of HS RBC membrane surface area due to specific molecular defects in several membrane proteins (␣ or ␤ spectrin, ankyrin, protein 4.2, and protein band 3), which result in the loss of cohesion between the lipid bilayer and the membrane skeleton. 10,11,14,15 The loss of membrane surface area results in the transformation of the biconcave discoid shape, first to a stomatocyte and finally to a spherocyte, with a progressive reduction in cellular deformability.Although a major role for the spleen in pathogenesis of HS is well established, 16 there are currently no data on the quantitative relationship between the extent of surface area loss and the extent of splenic entrapment. The only indirect evidence comes from early studies documenting reduced survival of Cr 51 -labeled spherocytes infused into healthy recipients, whereas the survival of normal RBCs in HS subjects was normal. [17][18][19] This implied that the reduced life span and splenic entrapment was an intrinsic feature of HS RBCs. Unfortunately, because neither the surface area nor the S/V ratio of infused spherocytes was measured in these studies, the extent of membrane surface area loss (or reduced S/V ratio) that leads to splenic retention of altered RBCs remains undefined. As a result, there is no predictive biologic parameter with which to estimate the risk of splenic entrapment of spherocytic cells and the ensuing anemia. Previously, we addressed this important issue using the isolated human spleen system 20 perfused with human RBCs with defined extents of surface area loss.RBCs with defined loss in membrane surface area can be generated experimentally by treatment with lysophosphatidylcholine (LPC). 6,7 By initially accumulating exclusively in the external leaflet of the RBC lipid bilayer, LPC induces in a dose-dependent manner echinocytosis There is an Inside Blood commentary on this article in this issue.The online version of this article contai...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen

Safeukui

Buffet

Deplaine

et al. 2012

Blood

118

139

View full text Add to dashboard Cite

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“…In normal erythrocytes, the Ca 2+ concentration increases transiently under shear stress-induced deformation during passage through narrow vessels and gradually increases during red cell senescence. 25,26 Under these conditions, scramblase is activated to scramble PS from the inner to outer leaflet, and the concerted effort of ATP11C and other flippases may not be sufficient to prevent Ca 2+ -activated PS externalization in these cells. Together, our findings imply that suppression of scramblase activity rather than flippase activity is the major contributor to maintenance of PS in the inner leaflet of normal erythrocytes and that PS externalization as an "eat-me signal" depends primarily on scramblase activity at the end of the erythrocytes' lifespan.…”

Section: Discussionmentioning

confidence: 99%

ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia

et al. 2016

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Phosphatidylserine is localized exclusively to the inner leaflet of the membrane lipid bilayer of most cells, including erythrocytes. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized phosphatidylserine is a phagocytic signal for splenic macrophages. Flippases are P-IV ATPase family proteins that actively transport phosphatidylserine from the outer to inner leaflet. It has not yet been determined which of the 14 members of this family of proteins is the flippase in human erythrocytes. Herein, we report that ATP11C encodes a major flippase in human erythrocytes, and a genetic mutation identified in a male patient caused congenital hemolytic anemia inherited as an X-linked recessive trait. Phosphatidylserine internalization in erythrocytes with the mutant ATP11C was decreased 10-fold compared to that of the control, functionally establishing that ATP11C is a major flippase in human erythrocytes. Contrary to our expectations phosphatidylserine was retained in the inner leaflet of the majority of mature erythrocytes from both controls and the patient, suggesting that phosphatidylserine cannot be externalized as long as scramblase is inactive. Phosphatidylserine-exposing cells were found only in the densest senescent cells (0.1% of total) in which scramblase was activated by increased Ca 2+ concentration: the percentage of these phosphatidylserine-exposing cells was increased in the patient's senescent cells accounting for his mild anemia. Furthermore, the finding of similar extents of phosphatidylserine exposure by exogenous Ca 2+ -activated scrambling in both control erythrocytes and the patient's erythrocytes implies that suppressed scramblase activity rather than flippase activity contributes to the maintenance of phosphatidylserine in the inner leaflet of human erythrocytes.

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“…18 It is well known that several types of mechanical stress impair erythrocyte filterability through the action of Ca 2+ -mediated signal transduction; mechanical stress on the erythrocyte membrane causes transmembrane Ca 2+ entry and impairs erythrocyte deformability. 7,21,22 Many investigations have demonstrated that arterial resistance, 23,24 and hence the blood flow shear rate, 25 is elevated in young SHR prior to the development of hypertension. Moreover, the erythrocyte free Ca 2+ concentration and transmembrane Ca 2+ influx are increased in SHR relative to WKY.…”

Section: Mechanisms Of Impaired Filterabilitymentioning

confidence: 99%

Impaired Erythrocyte Filterability of Spontaneously Hypertensive Rats: Investigation by Nickel Mesh Filtration Technique

Ariyoshi

Maruyama

Odashiro

et al. 2010

Circ J

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Induction of a Ca2+-activated K+ channel in human erythrocytes by mechanical stress

Cited by 38 publications

References 33 publications

Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen

Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen

ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia

Impaired Erythrocyte Filterability of Spontaneously Hypertensive Rats: Investigation by Nickel Mesh Filtration Technique

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