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Calcium homeostasis of human erythrocytes and its pathophysiological implications

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Summary

In human red cells, Ca is mainly bound to the inner side of the plasma membrane. A smaller part may be present within intracellular Ca storing vesicles, while only a few percent of total red cell Ca is in ionized form. In some hemolytic anemias (sickle cell anemia,Β-thalassemia), an increased number of endocytotic vesicles storing Ca is probably responsible for the elevation of total red cell Ca content. Red cell Ca inward transport, which is partially susceptible to inhibition by Ca entry blockers, has been reported to be enhanced by physiological shear stress and enrichment in membrane cholesterol, as well as in some hemolytic anemias. Normal intracellular ionized Ca levels have been assessed in several diseases where elevated Ca inward transport rates or decreased Ca efflux through the Ca pump (hemolytic anemias, cystic fibrosis, essential hypertension) had been observed previously. Thus, red cell Ca homeostasis is apparently capable of keeping ionized Ca levels within the physiological range of 20–60 nM under most pathological conditions investigated so far.

Conceptually, changes in red cell Ca homeostasis (or also in other red cell membrane parameters) may be of pathophysiological importance in two respects:

  1. 1)

    A disturbance may be directly responsible for some of the symptoms associated with a disease. This is the case in sickle cell anemia, where red cell dehydration is possibly caused by transient elevations of intracellular ionized calcium, which may activate K efflux through the Ca-activated K channel. The presence of dehydrated red cells will, in turn, lead to microvascular occlusion, a pathophysiologically important phenomenon in sickle cell anemia.

  2. 2)

    A disturbance seen in erythrocytes or other blood cells such as platelets or lymphocytes may reflect similar phenomena in other cell types known to be involved in pathophysiological mechanisms. A widespread, generalized membrane defect has been proposed to be present in essential hypertension, causing an alteration of cellular Ca (and Na) homeostasis [35]. In some cell types, these alterations of Ca homeostasis may affect important Ca-dependent intracellular processes such as vascular smooth muscle contraction, transmitter release, or cell proliferation.

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Abbreviations

ATP:

adenosine triphosphate

Ca-ATPase:

calcium-adenosine triphosphatase

DIDS:

4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid

HDL:

high density lipoprotein

NMR:

nuclear magnetic resonance

UEA1 :

Ulex europaeus agglutinin I

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  1. Physiologisches Institut der UniversitÄt München, FRG

    B. Engelmann

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Engelmann, B. Calcium homeostasis of human erythrocytes and its pathophysiological implications. Klin Wochenschr 69, 137–142 (1991). https://doi.org/10.1007/BF01665851

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