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(+)-Ca(2+) 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.
Goldhaber
Joshua I
JI
Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. jgoldhaber@mednet.ucla.edu
Henderson
Scott A
SA
Reuter
Hannes
H
Pott
Christian
C
Philipson
Kenneth D
KD
D000818:Animals; D006332:Cardiomegaly / Q000235:genetics*; D004594:Electrophysiology; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000235:genetics / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*
D019831:Sodium-Calcium Exchanger