Effects of Na+-Ca2+ Exchange Expression on Excitation-Contraction Coupling in Genetically Modified Mice

: We have created genetically altered mice to investigate how expression of the Na+‐Ca2+ exchange protein alters excitation‐contraction (E‐C) coupling. Whereas low levels of exchanger overexpression have minimal effects on E‐C coupling properties, high levels of overexpression in homozygous animals results in susceptibility to hypertrophy and heart failure, along with a significant reduction in E‐C coupling gain. While global knockout of the exchanger in mice is embryonic‐lethal, conditional knockout mice live to adulthood. Cardiac function is surprisingly normal in seven‐week‐old mice, but E‐C coupling gain is apparently increased. Thus, genetic modification of exchanger expression has a major influence on E‐C coupling.