Ca2+ Regulation of Ion Transport in the Na+/Ca2+ Exchanger

The binding of Ca2+ to two adjacent Ca2+-binding domains, CBD1 and CBD2, regulates ion transport in the Na+/Ca2+ exchanger. As sensors for intracellular Ca2+, the CBDs form electrostatic switches that induce the conformational changes required to initiate and sustain Na+/Ca2+ exchange. Depending on the presence of a few key residues in the Ca2+-binding sites, zero to four Ca2+ ions can bind with affinities between 0.1 to 20 mu M. Importantly, variability in CBD2 as a consequence of alternative splicing modulates not only the number and affinities of the Ca2+-binding sites in CBD2 but also the Ca2+ affinities in CBD1.