title: 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(+)-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.
authors.affiliation: Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. jgoldhaber@mednet.ucla.edu
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Goldhaber
authors.forename: Scott A
authors.initials: SA
authors.lastname: Henderson
authors.forename: Hannes
authors.initials: H
authors.lastname: Reuter
authors.forename: Christian
authors.initials: C
authors.lastname: Pott
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Philipson
mesh_terms: 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*
chemical_list: D019831:Sodium-Calcium Exchanger