Passive Cation Fluxes in Red Cell Membranes

Lew, Virgilio L.; Beaugé, Luis

doi:10.1007/978-3-642-46375-4_3

Cited by 42 publications

(34 citation statements)

References 91 publications

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“…53 In the context of the age-decline hypothesis, the broad PMCA V max variation pattern points toward a progressive fall in pump activity throughout the life of the mature cell. The possible mechanism of V max declines with cell age, such as progressive protease-induced falls in viable pump units per cell, 54 metabolically-linked, 15,47 progressive glycation, 55 or other, remains speculative. The method applied here to study the distribution of PMCA V max , by enabling the segregation of RBCs with different V max values, may provide a way to investigate the possible age-V max relation more directly in the future.…”

Section: Discussionmentioning

confidence: 99%

“…Elevated [Ca 2ϩ ] i has also been implicated in the activation of cell proteases and in the cross-linking of cytoskeletal proteins, with cumulative effects on cell aging and viability. [11][12][13][14][15] The first indirect evidence of substantial cell-to-cell variations in PMCA V max arose when Tiffert et al 16 examined the dehydration response of RBCs uniformly permeabilized to Ca 2ϩ with the ionophore A23187. As Ca 2ϩ influx into RBCs was progressively increased by increasing the ionophore concentration in a stepwise manner, RBCs suspended in plasmalike media dehydrated following an all-or-none rather than a graded pattern: Instead of all cells dehydrating at progressively faster rates-as expected with a uniform response-only a fraction of RBCs dehydrated and this fraction increased with increasing Ca 2ϩ influx.…”

Section: Introductionmentioning

confidence: 99%

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Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells

Lew

Daw

Perdomo

et al. 2003

Blood

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IntroductionThe plasma membrane Ca 2ϩ pump (PMCA), in its various isoforms, is expressed in all animal cells, where it plays a major role in the control of resting intracellular-free Ca 2ϩ levels ([Ca 2ϩ ] i ). [1][2][3][4] The PMCA was originally discovered and extensively studied in human red blood cells (RBCs) in which it is the only active Ca 2ϩ extrusion transporter. The maximal Ca 2ϩ transport capacity (V max ) of the PMCA in human RBCs (approximately 10 mmol [340 g hemoglobin {Hb}] Ϫ1 h Ϫ1 ) is high compared with the normal pump-leak turnover rate of Ca 2ϩ (approximately 50 mol [340 g Hb] Ϫ1 h Ϫ1 ). 3 Although early work indicated that Ca 2ϩ pump activity may vary from cell to cell over a much broader range than any other known hematologic parameter, 5 available measurements of PMCA V max in intact RBCs always reported mean values in the RBC population 6 ; the actual distribution of PMCA V max activity among RBCs was unknown. The aim of the present work was to characterize the distribution of PMCA V max activity in normal human RBCs.It is important to ascertain the extent of PMCA V max variation among RBCs because differences in pump-leak [Ca 2ϩ ] i levels may determine the degree of vulnerability of individual cells to certain physiologic and pathologic stresses. Human RBCs express in their plasma membrane a Ca 2ϩ -sensitive K ϩ channel (the "Gardos" channel 7-9 ). Hoffman et al 10 recently showed that the isoform hSK4 represents the small conductance Gardos channel of human RBCs. In conditions with elevated [Ca 2ϩ ] i , Gardos channel activation causes rapid net loss of KCl and water, leading to irreversible cell dehydration. Elevated [Ca 2ϩ ] i has also been implicated in the activation of cell proteases and in the cross-linking of cytoskeletal proteins, with cumulative effects on cell aging and viability. [11][12][13][14][15] The first indirect evidence of substantial cell-to-cell variations in PMCA V max arose when Tiffert et al 16 examined the dehydration response of RBCs uniformly permeabilized to Ca 2ϩ with the ionophore A23187. As Ca 2ϩ influx into RBCs was progressively increased by increasing the ionophore concentration in a stepwise manner, RBCs suspended in plasmalike media dehydrated following an all-or-none rather than a graded pattern: Instead of all cells dehydrating at progressively faster rates-as expected with a uniform response-only a fraction of RBCs dehydrated and this fraction increased with increasing Ca 2ϩ influx. Further experiments showed that Gardos channel activity among the RBCs was fairly uniform and could not have accounted for this all-or-none pattern. 17 These results suggested that uniform Ca 2ϩ permeabilization of RBCs did not generate uniformly elevated [Ca 2ϩ ] i among the cells and that the differences arose from variations in Ca 2ϩ pump activity.Further evidence for marked variations in Ca 2ϩ pump activity among RBCs from single donors was provided by 19 who detected large differences in the total Ca 2ϩ content of RBCs ([Ca T ] i ) uniformly permeabilized to ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells

Lew

Daw

Perdomo

et al. 2003

Blood

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show abstract

“…This points out a potentially more general property of transitional cells, or of cells in transitional developmental stages. In such states, the transport systems that normally secure the high osmotic stability of mature cells (25,48) may be overridden by transient transporters required for specific developmental needs (49). This would render transitional cells more vulnerable than the mature cell products to permeabilizing membrane injuries or environmental changes.…”

Section: Discussionmentioning

confidence: 99%

A mathematical model of the volume, pH, and ion content regulation in reticulocytes. Application to the pathophysiology of sickle cell dehydration.

Lew

Freeman²,

Ortiz³

et al. 1991

J. Clin. Invest.

100

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We developed a mathematical model of the reticulocyte, seeking to explain how a cell with similar volume but much higher ionic traffic than the mature red cell (RBC) regulates its volume, pH, and ion content in physiological and abnormal conditions. Analysis of the fluxbalance required by reticulocytes to conserve volume and composition predicted the existence of previously unsuspected Na '-dependent Cl -entry mechanisms.

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“…A similar membrane modification affected the The presence and rapid decline of the high K + leak fluxes in the newly formed cells may be rationalized in terms of a unified pump-leak concept (Tosteson and Hoffman, 1960;Lew and Beauge, 1978). However, the fact that the initially augmented leak was not affected by anti-L speaks against this concept, and we have shown earlier that the pump-and leak-associated L antigens may be immunologically and functionally separated (Lauf et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

LK sheep reticulocytosis: effect of anti-L on K influx and in vitro maturation.

Kim¹,

Theg²,

Lauf³

1980

The Journal of General Physiology

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After massive hemorrhage, adult sheep with genotypically low potassium (LK) red cells temporarily produce high potassium (HK) cells with ouabain-sensitive K + pump fluxes equivalent to mature HK red cells. In light of recent reports of different red cell volume populations accompanying the HK-LK transition also occurring in newborn LK sheep and the unresolved controversy over the effect of anti-L on K + transport in these immature red cells, we have reexamined the K + transport changes and the effect of anti-L in the newly formed HK cells at various times after anemic stress and under in vitro conditons. We found that ~7 d after bleeding, maximum reticulocytosis occurred in the peripheral blood. After separation by density centrifugation, the top 10% cell fraction contained 100% reticulocytes, with a mean cell volume 2.5 times larger than that of mature erythrocytes. These immature red cells were of HK type, and their K + pump and leak fluxes were 30 and 10 times higher, respectively, than those found in mature LK cells. The new cells may possess HK-and LK-type pumps because K + pump influx was significantly stimulated by anti-L. When separated by density centrifugation on days 9, 17, and 23 after bleeding, some of the cells apparently maintained their large size while gaining higher density. Large cells from day 9, kept in vitro for 22 h, showed anti-Lsensitive K + pump and leak fluxes that declined within hours, paralleling the behavior of these cells in vivo, whereas cellular K + levels changed much less. It is concluded that the newly formed red cells may belong to a stress-induced macrocytic cell population that does not acquire all of the characteristics of adult LK cells.

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Passive Cation Fluxes in Red Cell Membranes

Cited by 42 publications

References 91 publications

Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells

Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells

A mathematical model of the volume, pH, and ion content regulation in reticulocytes. Application to the pathophysiology of sickle cell dehydration.

LK sheep reticulocytosis: effect of anti-L on K influx and in vitro maturation.

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