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Research Article Free access | 10.1172/JCI110063

Separate Mechanisms of Deformability Loss in ATP-depleted and Ca-loaded Erythrocytes

Margaret R. Clark, Narla Mohandas, Claude Feo, Mark S. Jacobs, and Stephen B. Shohet

Cancer Research Institute, University of California, San Francisco, California 94143

Department of Medicine, University of California, San Francisco, California 94143

Department of Laboratory Medicine, University of California, San Francisco, California 94143

Institut de Pathologie Cellulaire, Hopital Bicetre, 94270 Kremlin Bicetre, France

Find articles by Clark, M. in: PubMed | Google Scholar

Cancer Research Institute, University of California, San Francisco, California 94143

Department of Medicine, University of California, San Francisco, California 94143

Department of Laboratory Medicine, University of California, San Francisco, California 94143

Institut de Pathologie Cellulaire, Hopital Bicetre, 94270 Kremlin Bicetre, France

Find articles by Mohandas, N. in: PubMed | Google Scholar

Cancer Research Institute, University of California, San Francisco, California 94143

Department of Medicine, University of California, San Francisco, California 94143

Department of Laboratory Medicine, University of California, San Francisco, California 94143

Institut de Pathologie Cellulaire, Hopital Bicetre, 94270 Kremlin Bicetre, France

Find articles by Feo, C. in: PubMed | Google Scholar

Cancer Research Institute, University of California, San Francisco, California 94143

Department of Medicine, University of California, San Francisco, California 94143

Department of Laboratory Medicine, University of California, San Francisco, California 94143

Institut de Pathologie Cellulaire, Hopital Bicetre, 94270 Kremlin Bicetre, France

Find articles by Jacobs, M. in: PubMed | Google Scholar

Cancer Research Institute, University of California, San Francisco, California 94143

Department of Medicine, University of California, San Francisco, California 94143

Department of Laboratory Medicine, University of California, San Francisco, California 94143

Institut de Pathologie Cellulaire, Hopital Bicetre, 94270 Kremlin Bicetre, France

Find articles by Shohet, S. in: PubMed | Google Scholar

Published February 1, 1981 - More info

Published in Volume 67, Issue 2 on February 1, 1981
J Clin Invest. 1981;67(2):531–539. https://doi.org/10.1172/JCI110063.
© 1981 The American Society for Clinical Investigation
Published February 1, 1981 - Version history
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Abstract

Membrane rigidity has been widely accepted as the dominant cause of reduced deformability both of ATP-depleted erythrocytes and erythrocytes containing excess calcium (Ca). However, recent studies have shown normal membrane deformability in ATP-depleted erythrocytes. In addition, Ca accumulation causes massive ion and water loss, and it has been shown that extensive dehydration causes an increase in intracellular viscosity with attendant loss of whole cell deformability. To obtain a detailed understanding of the processes accompanying ATP depletion and/or Ca accumulation that limit cell deformability, we have used a viscodiffractometric method to identify the cellular factors contributing to reduced whole cell deformability.

Analysis of the influence of the suspending medium osmolality on deformability showed the presence of two independent processes. One was a Ca-independent reduction in cell surface area/volume ratio, resulting from the spheroechinocyte formation that follows total ATP consumption. The other was a Ca-dependent increase in intracellular viscosity resulting from a Ca-induced loss of intracellular potassium and water. This deformability loss due to increased intracellular viscosity was found for cells depleted of ATP in the presence of Ca and in cells treated with Ca and A23187 without prior depletion. Ionophore-treated cells at high Ca concentration (>500 μM) formed spheroechinocytes with reduced surface area and a further loss of whole cell deformability. The rate of deformability loss associated with Ca-induced spheroechinocytosis was much more rapid than that associated with ATP-depletion-induced spheroechinocytosis, suggesting different mechanisms for the morphologic changes. No major effects of altered membrane elasticity on the reduced deformability of either ATP-depleted or Ca-loaded cells were observed.

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