Intracellular Ionic and Metabolic Regulation of Squid Nerve Na+/Ca2+ Exchanger
Intracellular Na+ and H+ synergistically inhibit the squid Na+/Ca2+ exchanger by reducing the affinity for Ca2+ of its regulatory site. MgATP antagonizes H+i and Na+i inhibition; this effect must occur through a phosphorylation-dephosphorylation process, because exogenous protein phosphatases prevent MgATP activation of the exchanger. Protection by ATP against H+i and Na+i inhibition happens by decreasing the apparent affinity for the synergistic binding of these cations to the carrier. In this way ATP modifies the apparent affinity for Ca2+ of its regulatory site. Mg2+ ions play an important role in the process because they are essential for ATP activation of Na+/Ca2+ exchange but can also promote deactivation of the ATP upregulated exchanger. At constant [ATP], activation at low [Mg2+]i is followed by deactivation as [Mg2+]i is increased. The most likely explanation for deactivation is stimulation of endogenous phosphatases. We developed a kinetic model that predicts all H+i, Na+i, and MgATP described above. This scheme includes the following conditions
squid nerve na+/ca2+ exchanger mgatp mg2+ ions h+ and na+ inhibition