Cell volume and drug action: Some interactions and perspectives

Rasgado-Flores, Héctor; Peña‐Rasgado, C.; Ehrenpreis, Seymour

doi:10.1002/ddr.430360202

Cited by 4 publications

References 168 publications

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The Effect of Hemoglobin A and S on the Volume- and pH-Dependence of K-Cl Cotransport in Human Erythrocyte Ghosts

Vitoux

Beuzard²,

Brugnara

1999

Journal of Membrane Biology

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K-Cl cotransport is abnormally active in erythrocytes containing positively charged hemoglobins such as Hb S (SS: beta6 Glu --> Val) or Hb C (CC: beta6 Glu --> Lys). The relatively younger age of erythrocytes in these diseases cannot completely account for the increased K-Cl cotransport activity. It has been suggested that these positively charged Hb may interact with the K-Cl cotransport system or one of its regulators and induce changes in its functional activity. We report here data on the volume- and pH-dependence of K-Cl cotransport in ghosts obtained from normal and sickle erythrocytes, and on the effect of addition of either Hb A or Hb S before resealing. In erythrocyte ghosts prepared with the gel column method to contain minimal amounts of Hb, (white ghosts, WG), K-Cl cotransport has similar magnitude in normal and sickle erythrocytes, is not inhibited by alkaline pH and it is volume-independent. Addition of low concentrations of Hb A to WG from normal erythrocytes decreases the magnitude of K-Cl cotransport and restores its volume dependency, but not its pH sensitivity. Addition of Hb S to WG from either normal or sickle erythrocytes restores the volume-dependent component of K-Cl cotransport and increases the magnitude of flux mediated by this transporter. Thus, Hb A and Hb S seem to affect in different manners the functional properties of K-Cl cotransport.

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The Effect of Hemoglobin A and S on the Volume- and pH-Dependence of K-Cl Cotransport in Human Erythrocyte Ghosts

Vitoux

Beuzard²,

Brugnara

1999

Journal of Membrane Biology

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Reversible vacuolation of T-tubules in skeletal muscle: Mechanisms and implications for cell biology

Krolenko

Lucy

2001

International Review of Cytology

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et al. 2000

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To investigate the involvement of K+ efflux in apoptotic cell shrinkage, we monitored efflux of the K+ congener, 86Rb+, and cell volume during CD95-mediated apoptosis in Jurkat cells. An anti-CD95 antibody caused apoptosis associated with intracellular GSH depletion, a significant increase in 86Rb+ efflux, and a decrease in cell volume compared with control cells. Preincubating Jurkat cells with Val-Ala-Asp-chloromethylketone (VAD-cmk), an inhibitor of caspase proteases, prevented the observed 86Rb+ efflux and cell shrinkage induced by the anti-CD95 antibody. A wide range of inhibitors against most types of K+ channels could not inhibit CD95-mediated efflux of 86Rb+, however, the uptake of 86Rb+ by Jurkat cells was severely compromised when treated with anti-CD95 antibody. Uptake of 86Rb+ in Jurkat cells was sensitive to ouabain (a specific Na+/K(+)-ATPase inhibitor), demonstrating Na+/K(+)-ATPase dependent K+ uptake. Ouabain induced significant 86Rb+ efflux in untreated cells, as well as it seemed to compete with 86Rb+ efflux induced by the anti-CD95 antibody, supporting a role for Na+/K(+)-ATPase in the CD95-mediated 86Rb+ efflux. Ouabain treatment of Jurkat cells did not cause a reduction in cell volume, although together with the anti-CD95 antibody, ouabain potentiated CD95-mediated cell shrinkage. This suggests that the observed inhibition of Na+/K(+)-ATPase during apoptosis may also facilitate apoptotic cell shrinkage.

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Cell volume and drug action: Some interactions and perspectives

Abstract: lllinois Q 1995 w i f c y -~m , Inc.

Cited by 4 publications

References 168 publications

The Effect of Hemoglobin A and S on the Volume- and pH-Dependence of K-Cl Cotransport in Human Erythrocyte Ghosts

The Effect of Hemoglobin A and S on the Volume- and pH-Dependence of K-Cl Cotransport in Human Erythrocyte Ghosts

Reversible vacuolation of T-tubules in skeletal muscle: Mechanisms and implications for cell biology

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