Modulation of the Na+-Ca2+ antiport by its ionic environment: the effect of lithium.

The Na+-Ca2+ exchanger is a major Ca2+ transporting molecule in excitable cells. It is localized in the plasma membrane and participates in the regulation of intracellular Ca2+ concentration. Li+ starting at a concentration of 5 mM inhibits Na+-Ca2+ exchange in synaptic plasma membrane (SPM) vesicles. Both the initial rate and steady state levels of Na+-gradient-dependent Ca2+ transport are inhibited. Experiments studying the mechanism of Li+ inhibition revealed the following: no competition was observed between Li+ and Na+ on the binding site to the exchanger; the depolarization of the SPM obtained by K+ was considerably diminished in the presence of Li+; and 3) the affinity of Ca2+ to the Na+-Ca2+ exchanger decreased in the presence of Li+. Since the Na+-Ca2+ exchanger operates in an electrogenic fashion, the combined effects of reduced membrane polarization with the reduction in Ca2+ affinity can explain the inhibitory effect of Li+.