Calcium Extrusion Across the Plasma Membrane by the Calcium-Pump and the Ca2+-Na+ Exchange System

There is agreement that living cells keep the intracellular Ca2+ concentration far below that existing beyond the plasma membrane. Measuring the exceedingly low cytosolic free Ca2+ concentration is not an easy matter in cells surrounded by an extracellular fluid of 1 to 2 mM Ca2+ concentration and containing intracellular storage organelles and cation-binding structures that bristle with calcium. In the rather rare instances where reliable estimates exist, the unprepared observer finds reason to marvel: the figure is in the 10 nM range in nerve, muscle, myocardium, and human red cells. The elementary fact that cells maintain the cytosolic Ca2+ concentration so far below the external concentration (1.3 mM in the extracellular space of land-living mammals and 10 mM in seawater) is pertinent to most of the topics discussed in this volume. It is at the basis of the ability of cells to use calcium as a mediating link between various stimuli at the cell surface and intracellular events known to be the physiological consequences of such stimuli. The signaling by calcium is invariably achieved by an increase of the passive permeability across specific, gated channels in the plasma membrane or the membrane of intracellular organelles that contain calcium at high concentration, such as the sarcoplasmic reticulum. Not only has the calcium entering the cytosol during such activation to be removed, but there is in all cells a resting net influx of calcium that must be balanced by an equal efflux if the Ca2+ gradient across the plasma membrane is to be maintained. Storage organelles can remove some calcium at short notice, but it goes without saying that in the long run only calcium-exporting systems will keep the cytosol free of Ca2+. In parenthesis, the reader may be reminded that the plasma membrane calcium transport also serves the purpose of transcellular uphill calcium translocation, certainly in epithelial structures and possibly in bone cells.