Ionic Selectivity of NCKX2, NCKX3, and NCKX4 for Monovalent Cations at K+-Binding Site

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To determine the ionic selectivity of K+-sites in three members of Na+/Ca2++K+ exchanger (NCKX) family: NCKX2, NCKX3 and NCKX4, we compared the amplitudes of reverse mode NCKX current (INCKX) activated by K+-substitutes (Rb+, NH4+, Cs+, or Li+) relative to that by K+ in an HEK293 cell overexpressing each of NCKX isoforms. In all three isoforms, monovalent cations activated INCKX with similar order of potency: K+ > Rb+ > NH4+ > Cs+ ≫ Li+. However, the relative potency of Cs+ and NH4+ for activating NCKX2 was significantly higher than those for NCKX3 and NCKX4, indicating that the selectivity of NCKX2 for K+ is weaker than the other two isoforms.

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