The sodium-calcium exchanger (NCX) is a transmembrane protein that exchanges one calcium ion per three sodium ions. The direction of ion flux is dependent on a number of factors including pH, sodium concentrations, Ca2+ concentrations, and ATP levels. Under physiological conditions, the major driving force of these exchangers is the Na+ gradient created by the Na+/K+ ATPase. However, the direction of ion flux is reversible, and high intracellular Na+ levels can cause Ca2+ influx with Na+ extrusion. Increasing intracellular Ca2+ can lead to cell death through mechanisms described above. In cells, NCX is found in the plasma membrane, mitochondria, and endoplasmic reticulum. Various isoforms of NCX exist, including NCX1, NCX2, NCX3, and NCX4.
