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Effects of Na + ‐Ca 2+ Exchange Expression on Excitation‐Contraction Coupling in Genetically Modified Mice
Author(s) -
GOLDHABER JOSHUA I.,
HENDERSON SCOTT A.,
REUTER HANNES,
POTT CHRISTIAN,
PHILIPSON KENNETH D.
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1341.011
Subject(s) - excitation–contraction coupling , coupling (piping) , knockout mouse , chemistry , medicine , endocrinology , conditional gene knockout , microbiology and biotechnology , biology , myocyte , biochemistry , materials science , gene , phenotype , metallurgy
A bstract : 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.