In the squid axon Na+/Ca2+ exchanger the state of the Cai-regulatory site influences the affinities of the intra- and extracellular transport sites for Na+ and Ca2+

In squid axons, intracellular Mg2+ reduces the activity of the Na+/Ca2+ exchanger by competing with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{Ca}}_{\text{i}}^{{\text{2 + }}} $$\end{document} for its regulatory site. The state of the Cai-regulatory site (active–inactive) also alters the apparent affinity of intra- and extracellular transport sites. Conditions that hinder the binding of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{Ca}}_{\text{i}}^{{\text{2 + }}} $$\end{document} (low pHi, low [Ca2+]i, high [Mg2+]i) diminish the apparent affinity of intracellular transport sites, in particular for Nai due to its synergism with H+ inhibition, but less noticeably for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{Ca}}_{\text{i}}^{{\text{2 + }}} $$\end{document} because of its antagonism towards (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{H}}_{\text{i}}^{\text{ + }} {\text{ + Na}}_{\text{i}}^{\text{ + }} $$\end{document}) and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{Mg}}_{\text{i}}^{{\text{2 + }}} $$\end{document} inhibitions. These are kinetic effects unrelated to the true affinity of the sites. With the Cai-regulatory site saturated, the intracellular transporting sites are insensitive to [H+]i and to ATP. Likewise, the state of the Cai-regulatory site (activated or inactivated) influences the affinity of the extracellular Cao and Nao-transport sites (trans effects). In this case, the effects are opposite to those predicted by any of the transport schemes proposed for the Na+/Ca2+exchanger; i.e. its mechanism remains unexplained. In addition to their intrinsic importance for a full understanding of the properties of the Na+/Ca2+ exchanger, these findings show a new way by which the state of the Cai-regulatory site may determine net movements of Ca2+ through this system.