Human erythrocyte membranes exhibit a cooperative calmodulin-dependent Ca2+-ATPase of high calcium sensitivity

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

External organisations

  • Birmingham University
  • Department of Biochemistry

Abstract

It is thought that the ionized Ca2+ concentration in the cytosol of healthy erythrocytes is in the range 0.01-0.1 μM (ref. 1) and that this low concentration is maintained by an ATP-driven calmodulin-dependent Ca 2+ pump in the plasma membrane2,3. The Ca 2+-stimulated ATPase which is the enzymatic expression of this pump varies in its calcium sensitivity between different preparations of erythrocyte ghosts, with activation generally occurring in a concentration range between ∼1 and 10 μM Ca2+ (refs 2-5). This is a higher range of Ca2+ concentrations than might be anticipated for activation of a pump that sustains intracellular concentrations of Ca2+ below 0.1 μM, and recent reports have suggested activation in some membrane preparations at Ca2+ concentrations in the range 0.1-1.0 μM (refs 6, 7). We report here a simple method for preparing human erythrocyte membranes in 2.5 mM HEPES/1 mM EGTA at pH 7.0 (see Fig. 1 legend) in which the activation of the Ca2+-ATPase by Ca2+ and intracellular concentrations of calmodulin is highly cooperative and is complete by ∼1 μM Ca2+. Unlike other available erythrocyte membrane preparations, the pattern of activation by Ca2+ and calmodulin is not complicated by partial resealing of the ghosts during and after isolation. We suggest that this cooperative activation of the Ca2+ pump may explain how healthy erythrocytes maintain their normal cytosol Ca2+ concentration at a threshold value at or below ∼0.1 μM. We also note that several other calmodulin-dependent enzymes display similar cooperative activation kinetics.

Details

Original languageEnglish
Pages (from-to)270-271
Number of pages2
JournalNature
Volume290
Issue number5803
Publication statusPublished - 1 Dec 1981

ASJC Scopus subject areas