Effects of Na+-Ca2+ Exchange Expression on Excitation-Contraction Coupling in Genetically Modified Mice
Abstract: 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.
cardiac excitation-contraction coupling cre-lox l-type calcium current sodium-calcium exchange transgenic mice