Introduction of a positive charge at position 516 or 683 partially rescues NCX Ca2+ regulation. Previously we have shown that NCX mutants E516L, D578V, and E683V lack Ca2+ regulation. Introduction of a positive charge at any of these positions partially restores NCX Ca2+ regulation. A, outward currents recorded from oocytes expressing the indicated construct. B, Peak current values versus cytoplasmic Ca2+ for WT (■), E516R (□), and E683R (●). C, fractional activity values measured at different Ca2+ concentrations for each exchanger.