Na+/Ca2+ exchanger knockout mice: plasticity of cardiac excitation-contraction coupling.

The Na+/Ca2+ exchanger (NCX) is the main Ca2+ extrusion mechanism of the cardiac myocyte. Nevertheless, cardiac-specific NCX knockout (KO) mice are viable to adulthood. We have identified two adaptations of excitation-contraction coupling (ECC) to the absence of NCX in these animals: (a) a reduction of the L-type Ca2+ current (I(Ca)) with an increase in ECC gain and (b) a shortening of the action potential (AP) to further limit Ca2+ influx. Both mechanisms contribute to Ca2+ homeostasis by reducing Ca2+ influx while maintaining contractility. These adaptations may comprise important feedback mechanisms by which cardiomyocytes may be able to limit Ca2+ influx in situations of compromised Ca2+ extrusion capacity.