Erythrocyte cation permeability induced by mechanical stress: a model for sickle cell cation loss

Johnson, Robert M.; Gannon, Susan

doi:10.1152/ajpcell.1990.259.5.c746

Cited by 36 publications

(19 citation statements)

References 26 publications

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“…Previous studies, performed under somewhat different conditions, suggested that application of shear stress can cause leakiness to calcium (13). The leak pathway we have studied is not calcium dependent (6,9), indicating that if calcium does gain entry during deformation it does not reach levels able to stimulate calcium-activated K channels. Whether calcium in lesser amounts is entering RBC during our studies is not determined yet.…”

Section: Discussioncontrasting

confidence: 45%

“…It is fully reversible so that cells return to their normal state upon cessation of deformation (6). The leak is balanced so that induced Na influx equals K efflux, it is lower at low pH, and it is not chloride dependent (6,9). Previous studies, performed under somewhat different conditions, suggested that application of shear stress can cause leakiness to calcium (13).…”

Section: Discussionmentioning

confidence: 99%

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Reversible deformation-dependent erythrocyte cation leak. Extreme sensitivity conferred by minimal peroxidation

Hebbel

Mohandas

1991

Biophysical Journal

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To determine the threshold at which red blood cells (RBC) begin to manifest deformation-dependent leakiness to monovalent cations, we examined net passive potassium leak during elliptical deformation. Normal RBC did not begin to leak appreciable amounts of potassium until shear stress reached 204 dyn/cm2, at which point they had attained greater than 96% of their maximal deformation. In striking contrast, RBC that had undergone minimal, physiologically relevant degrees of peroxidative damage induced by t-butylhydroperoxide began to leak potassium at only 59 dyn/cm2 when they had reached only 63% of their maximal deformation. The cation leak identified in this manner is not prelytic, and it is fully reversible. Therefore, these data may be relevant to abnormal cation leaks that develop in sickle red cells that have membranes damaged by auto-oxidative stress and that manifest an exuberant but reversible leakiness to monovalent cation during sickling-induced deformation of the cell membrane.

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Section: Discussioncontrasting

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Reversible deformation-dependent erythrocyte cation leak. Extreme sensitivity conferred by minimal peroxidation

Hebbel

Mohandas

1991

Biophysical Journal

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“…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%

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

Safeukui

Buffet

Deplaine

et al. 2012

Blood

122

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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“…Physiological shear stress in the circulation has been claimed to cause a reversible increase in Ca 2+ permeability[6], [7], [8], [9], [10]. Recent evidence supported the view that the increasing density of aging human RBCs, attributed to a progressive loss of KCl and osmotic water, results from the cumulative effects of declining Ca 2+ extrusion capacity of the plasma membrane Ca 2+ pump, aided by minor episodes of increased Ca 2+ permeability in the circulation [11], [12], [13], [14], [15].…”

Section: Introductionmentioning

confidence: 99%

Local Membrane Deformations Activate Ca2+-Dependent K+ and Anionic Currents in Intact Human Red Blood Cells

et al. 2010

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BackgroundThe mechanical, rheological and shape properties of red blood cells are determined by their cortical cytoskeleton, evolutionarily optimized to provide the dynamic deformability required for flow through capillaries much narrower than the cell's diameter. The shear stress induced by such flow, as well as the local membrane deformations generated in certain pathological conditions, such as sickle cell anemia, have been shown to increase membrane permeability, based largely on experimentation with red cell suspensions. We attempted here the first measurements of membrane currents activated by a local and controlled membrane deformation in single red blood cells under on-cell patch clamp to define the nature of the stretch-activated currents.Methodology/Principal FindingsThe cell-attached configuration of the patch-clamp technique was used to allow recordings of single channel activity in intact red blood cells. Gigaohm seal formation was obtained with and without membrane deformation. Deformation was induced by the application of a negative pressure pulse of 10 mmHg for less than 5 s. Currents were only detected when the membrane was seen domed under negative pressure within the patch-pipette. K+ and Cl− currents were strictly dependent on the presence of Ca2+. The Ca2+-dependent currents were transient, with typical decay half-times of about 5–10 min, suggesting the spontaneous inactivation of a stretch-activated Ca2+ permeability (PCa). These results indicate that local membrane deformations can transiently activate a Ca2+ permeability pathway leading to increased [Ca2+]i, secondary activation of Ca2+-sensitive K+ channels (Gardos channel, IK1, KCa3.1), and hyperpolarization-induced anion currents.Conclusions/SignificanceThe stretch-activated transient PCa observed here under local membrane deformation is a likely contributor to the Ca2+-mediated effects observed during the normal aging process of red blood cells, and to the increased Ca2+ content of red cells in certain hereditary anemias such as thalassemia and sickle cell anemia.

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Erythrocyte cation permeability induced by mechanical stress: a model for sickle cell cation loss

Cited by 36 publications

References 26 publications

Reversible deformation-dependent erythrocyte cation leak. Extreme sensitivity conferred by minimal peroxidation

Reversible deformation-dependent erythrocyte cation leak. Extreme sensitivity conferred by minimal peroxidation

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

Local Membrane Deformations Activate Ca2+-Dependent K+ and Anionic Currents in Intact Human Red Blood Cells

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