Abstract
The Na$^+$/Ca$^2+$ exchanger (NCX) is the primary Ca$^2+$
extrusion mechanism in cardiomyocytes. To further investigate the
role of NCX in excitation-contraction coupling and Ca$^2+$ homeostasis,
we created murine models with altered expression levels of NCX. Homozygous
overexpression of NCX resulted in mild cardiac hypertrophy. Decline
of the Ca$^2+$ transient and relaxation of contraction were increased
and the reverse mode of NCX was augmented. Overexpression also led
to a higher susceptibility to ischemia-reperfusion injury and to
a greater ability of NCX to trigger Ca$^2+$-induced Ca$^2+$
release. Furthermore, an increase in peak L-type Ca$^2+$ current
was observed suggesting a direct influence of NCX on L-type Ca$^2+$
current. Whereas global knockout of NCX led to prenatal death, a
recently generated cardiac-specific NCX knockout mouse was viable
with surprisingly normal contractile properties. Expression levels
of other Ca$^2+$-handling proteins were not altered. Ca$^2+$
influx in these animals is limited by a decrease of peak L-type Ca$^2+$
current. An alternative Ca$^2+$ efflux mechanism, presumably
the plasma membrane Ca$^2+$-ATPase, is sufficient to maintain
Ca$^2+$-homeostasis in the NCX knockout mice.
- 15336980
- action
- animals,
- ca,
- calcium
- calcium,
- cardiac,
- cardiomegaly,
- contraction,
- disease,
- electrophysiology,
- energy
- exchanger,
- extramural,
- genetic
- gov't,
- homozygote,
- humans,
- hypertrophy,
- injury,
- isoproterenol,
- knockout,
- lcium,
- left
- metabolism,
- mice,
- myocardial
- myocardium,
- myocytes,
- n.i.h.,
- non-u.s.
- p.h.s.,
- phenotype,
- potentials,
- predisposition
- reperfusion
- research
- reticulum,
- sarcolemma,
- sarcoplasmic
- signaling,
- sodium,
- sodium-calcium
- support,
- to
- transgenic,
- u.s.
- ventricular,
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