Beschreibung:
<jats:p><jats:bold>A<jats:sc>bstract</jats:sc>: </jats:bold> Intracellular Na<jats:sup>+</jats:sup> and H<jats:sup>+</jats:sup> synergistically inhibit the squid Na<jats:sup>+</jats:sup>/Ca<jats:sup>2+</jats:sup> exchanger by reducing the affinity for Ca<jats:sup>2+</jats:sup> of its regulatory site. MgATP antagonizes H<jats:sup>+</jats:sup><jats:sub>i</jats:sub> and Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub> 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<jats:sup>+</jats:sup><jats:sub>i</jats:sub> and Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub> 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 Ca<jats:sup>2+</jats:sup> of its regulatory site. Mg<jats:sup>2+</jats:sup> ions play an important role in the process because they are essential for ATP activation of Na<jats:sup>+</jats:sup>/Ca<jats:sup>2+</jats:sup> exchange but can also promote deactivation of the ATP upregulated exchanger. At constant [ATP], activation at low [Mg<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> is followed by deactivation as [Mg<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> is increased. The most likely explanation for deactivation is stimulation of endogenous phosphatases. We developed a kinetic model that predicts all H<jats:sup>+</jats:sup><jats:sub>i</jats:sub>, Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub>, and MgATP described above. This scheme includes the following conditions: (i) The binding of Ca<jats:sup>2+</jats:sup> to the regulatory site is essential for the binding of Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub> or Ca<jats:sup>2+</jats:sup><jats:sub>i</jats:sub> to the transporting sites. (ii) The binding of a first H<jats:sup>+</jats:sup><jats:sub>i</jats:sub> to the carrier displaces Ca<jats:sup>2+</jats:sup><jats:sub>i</jats:sub> from its regulatory site and allows binding of one Na<jats:sup>+</jats:sup> forming a H.E<jats:sub>1</jats:sub>.Na complex. The H.E<jats:sub>1</jats:sub>.Na complex can bind a second H<jats:sup>+</jats:sup><jats:sub>i</jats:sub> forming a dead‐end inhibitory H<jats:sub>2</jats:sub>.E<jats:sub>1</jats:sub>.Na complex. (iii) MgATP, through an unspecified phosphorylation process, decreases the apparent affinity for the synergistic H<jats:sup>+</jats:sup><jats:sub>i</jats:sub> and Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub> binding to the carrier.</jats:p>