Key result
Cardiac-specific NCX knockout mice adapt to the absence of NCX by reducing L-type Ca2+ current with increased ECC gain and shortening the action potential to limit Ca2+ influx.
Cardiac-specific NCX knockout mice survive to adulthood through adaptations in excitation-contraction coupling that limit calcium influx while maintaining contractility.
NCX knockout adaptations in mice caution against clinical translation; leaves open whether similar compensation occurs in human cardiomyocytes.
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.
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Pott et al. (2007) studied Cardiac-specific NCX knockout. Cardiac-specific NCX knockout was evaluated on Adaptations of excitation-contraction coupling (ECC). Cardiac-specific NCX knockout mice adapt to the absence of NCX by reducing L-type Ca2+ current with increased ECC gain and shortening the action potential to limit Ca2+ influx.
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