Functional significance of Na+/Ca2+ exchangers co-localization with ryanodine receptors.

Co-localization of Na + /Ca 2+ exchangers (NCX) with ryanodine receptors (RyRs) is debated. We incorporate local NCX current in a biophysically detailed model of L-type Ca 2+ channels (LCCs) and RyRs and study the effect of NCX on the regulation of Ca 2+ -induced Ca 2+ release and the shape of the action potential. In canine ventricular cells, under pathological conditions, e.g., impaired LCCs, local NCXs become an enhancer of sarcoplasmic reticulum release. Under such conditions incorporation of local NCXs is critical to accurately capture mechanisms of excitation-contraction coupling.