SARCO ENDOPLASMIC RETICULUM CA2+-ATPASE ISOFORMS - DIVERSE RESPONSES TO ACIDOSIS/

The effects of acidic pH on the kinetics of Ca2+-ATPase isoforms from intracellular membranes of skeletal muscle, cardiac muscle, cerebellum and blood platelets were studied. At neutral pH, all four Ca2+-ATPase isoforms exhibited similar Ca2+-concentration requirements for half-m aximal rates of Ca2+ uptake and ATP hydrolysis. A decrease in the pH f rom 7.0 to 6.0 promoted a decrease in both the apparent affinity for C a2+ [increasing half-maximal activation (K-0.5)] and the maximal veloc ity (V-max) of Ca2+ uptake. With skeletal muscle vesicles these effect s were 5 to 10 times smaller than those observed with all the other is oforms. Acidification of the medium from pH 7.0 to 6.5 caused the rele ase of Ca2+ from loaded vesicles and a decrease in the amount of Ca2retained by the vesicles at the steady state. With the vesicles derive d from skeletal muscle these effects were smaller than for vesicles de rived from other tissues. The rate of passive Ca2+ efflux from skeleta l and cardiac muscle vesicles, loaded with Ca2+ and diluted in a mediu m containing none of the ligands of Ca2+-ATPase, was the same at pH 7. 0 and 6.0. In contrast, the rate of Ca2+ efflux from cerebellar and pl atelet vesicles increased 2-fold after acidification of the medium. Th e effects of DMSO, Mg2+ with P-i and arsenate on the rate of Ca2+ effl ux varied among the different preparations tested. The differences bec ame more pronounced when the pH of the medium was decreased from 7.0 t o 6.0. It is proposed that the kinetic differences among the Ca2+-ATPa se isoforms may reflect different adaptations to cellular acidosis, su ch as that which occurs during ischaemia.