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.
- 16093490
- action
- animals,
- ca,
- calcium,
- cardiac,
- cardiomegaly,
- contraction,
- disease,
- electrophysiology,
- energy
- exchanger,
- extramural,
- genetic
- gov't,
- homozygote,
- injury,
- isoproterenol,
- knockout,
- lcium,
- metabolism,
- mice,
- myocardial
- myocardium,
- myocytes,
- n.i.h.,
- non-u.s.
- p.h.s.,
- phenotype,
- potentials,
- predisposition
- reperfusion
- research
- sarcolemma,
- sodium,
- sodium-calcium
- support,
- to
- transgenic,
- u.s.
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