Multiple transport modes of the cardiac Na~+/Ca~(2+) exchanger

摘要

The cardiac Na~+/Ca~(2+) exchanger (NCX1; ref. 2) is a bi-directional Ca~(2+) transporter that contributes to the electrical activity of the heart. When, and if, Ca~(2+) is exported or imported depends on the Na~+/Ca~(2+) exchange ratio. Whereas a ratio of 3:1 (Na~+:Ca~(2+)) has been indicated by Ca~(2+) flux equilibrium studies, a ratio closer to 4:1 has been indicated by exchange current reversal potentials. Here we show, using an ion-selective electrode technique to quantify ion fluxes in giant patches, that ion flux ratios are approximately 3.2 for maximal transport in either direction. With Na~+ and Ca~(2+) on both sides of the membrane, net current and Ca~(2+) flux can reverse at different membrane potentials, and inward current can be generated in the absence of cytoplasmic Ca~(2+), but not Na~+. We propose that NCX1 can transport not only 1 Ca~(2+) or 3 Na~+ ions, but also 1 Ca~(2+) with 1 Na~+ ion at a low rate. Therefore, in addition to the major 3:1 transport mode, import of 1 Na~+ with 1 Ca~(2+) defines a Na~+-conducting mode that exports 1 Ca~(2+), and an electroneutral Ca~(2+) influx mode that exports 3 Na~+. The two minor transport modes can potentially determine resting free Ca~(2+) and background inward current in heart.