MgATP and phosphoinositides activate Na+/Ca2+ exchange in bovine brain vesicles. Comparison with other Na+/Ca2+ exchangers

We investigated the metabolic modulation of the Na+/Ca2+ exchanger in membrane vesicles obtained from bovine brain. The Na+/Ca2+ exchanger was activated by MgATP with a K0.5 of 336 µM. Unlike the squid nerve Na+/Ca2+ exchanger, this effect required no cytosolic component. Also, stimulation is the same in vesicles prepared and/or assayed at the ionic strength found in mammals (160 mM) or marine animals (300 mM). Other differences between squid and bovine nerve are that the bovine brain Na+/Ca2+ exchanger is not stimulated by phosphagens, either phosphoarginine (molluscan source) or phosphocreatine (mammalian source); and that stimulation by MgATP in bovine brain is related to the production of polyphosphatidylinositides. In this regard bovine heart and brain Na+/Ca2+ exchangers behave similarly. These results indicate that the mechanisms of metabolic regulation of the squid and mammalian nerve Na+/Ca2+ exchangers are not alike and represent differences between species. Some differences found between bovine heart and brain exchangers, such as MgATP stimulation even at saturating [Ca2+] and the smaller degree of activation by adenosine 5′-O-(3-thiotriphosphate) (ATP-γ-S) in the brain, may be related to the unequal isoform population in both tissues.