THE CALCIUM‐PUMPING ATPase OF HEART SARCOLEMMA *

Cell membrane Ca2+-pumping ATPases of the type first described for human erythrocytes' have been found in a number of eukaryotic cell types. They probably represent a general mechanism by which eukaryotic cells maintain a large transmembrane Caz+ electrochemical gradient. However, while a Ca2+ electrochemical gradient is found in a variety of cell types, there are marked differences with respect to the cell membrane Ca2+ fluxes. In excitable cells, CaZ+ entry mediates the coupling between an external stimulus and the intracellular response[s). As a consequence, the plasma membrane of excitable cells must be able to deal with large transient Ca2+ fluxes. Within this context, it is of special interest to investigate whether the plasma membrane of excitable cells contains an ATP-dependent Ca2+ pump, whether this pump has special properties, e.g., as compared with the erythrocyte (EC) Ca2+-ATPase, that would match the particular needs of the cell with respect to its CaZ+ fluxes, and whether there are other Ca2+-extruding mechanisms present in the cell membrane of excitable cells. This report will deal with the demonstration and characterization of an ATPdependent Ca2+ pump of heart sarcolemma. The heart cell membrane possesses a very active Na+/Ca2+ exchange system responsible for the extrusion of Ca2+.' Since the Na+/Ca2' exchange is electrogenic (Lea, at least 3 Na+ are exchanged for 1 Ca2+), the exchanger probably extrudes Caz+ from the heart cytosol when the cardiac membrane potential is more negative than 20 mV (inside n e g a t i ~ e ) . ~ However, the affinity (K,) of the exchanger for Ca2+ is between 2 and 10 pM (depending on the physiological state of the cell], and the binding of Ca" to the side of the exchanger facing the interior of the cell is markedly inhibited (competitively] by the presence of 5-7 mM Na'. Therefore, although the Na+/Ca2+ exchanger should be able to lower the resting level of free intracellular Ca2+ to below 0.1 pM at equilibrium (due to its electrogenic mode of operation and to a resting membrane potential of 80 mV negative inside], kinetic parameters might prevent its efficient functioning at free intracellular concentrations below the micromolar range. A high-affinity Ca2+pumping ATPase in heart sarcolemma might therefore play an important role in the relaxation process of the heart.