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+.
D000818:Animals; D001921:Brain / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects*; D008094:Lithium / Q000494:pharmacology*; D008564:Membrane Potentials; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism
D007473:Ion Channels; D008094:Lithium; D012964:Sodium; D002118:Calcium