The role of the Na + /Ca 2+ exchanger (NCX) as the main pathway for Ca 2+ extrusion from ventricular myocytes is well established. However, both the role of the Ca 2+ entry mode of NCX in regulating local Ca 2+ dynamics and the role of the Ca 2+ exit mode during the majority of the physiological action potential (AP) are subjects of controversy. The functional significance of NCXs location in T-tubules and potential co-localization with ryanodine receptors was examined using a local Ca 2+ control model of low computational cost. Our simulations demonstrate that under physiological conditions local Ca 2+ and Na + gradients are critical in calculating the driving force for NCX and hence in predicting the effect of NCX on AP. Under physiological conditions when 60% of NCXs are located on T-tubules, NCX may be transiently inward within the first 100ms of an AP and then transiently outward during the AP plateau phase. Thus, during an AP NCX current (I NCX ) has three reversal points rather than just one. This provides a resolution to experimental observations where Ca 2+ entry via NCX during an AP is inconsistent with the time at which I NCX is thought to become inward. A more complex than previously believed dynamic regulation of I NCX during AP under physiological conditions allows us to interpret apparently contradictory experimental data in a consistent conceptual framework. Our modelling results support the claim that NCX regulates the local control of Ca 2+ and provide a powerful tool for future investigations of the control of sarcoplasmic reticulum (SR) Ca 2+ release under pathological conditions.