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.
%0 Journal Article
%1 Pott_2004_1336
%A Pott, Christian
%A Goldhaber, Joshua I
%A Philipson, Kenneth D
%D 2004
%J Biochem. Biophys. Res. Commun.
%K 15336980 Action Animals, Ca, Calcium Calcium, Cardiac, Cardiomegaly, Contraction, Disease, Electrophysiology, Energy Exchanger, Extramural, Genetic Gov't, Homozygote, Humans, Hypertrophy, Injury, Isoproterenol, Knockout, 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, Transgenic, U.S. Ventricular, lcium, to
%N 4
%P 1336--1340
%R 10.1016/j.bbrc.2004.08.038
%T Genetic manipulation of cardiac Na$^+$/Ca$^2+$ exchange expression.
%U http://dx.doi.org/10.1016/j.bbrc.2004.08.038
%V 322
%X 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.
@article{Pott_2004_1336,
abstract = {The {N}a$^{+}$/{C}a$^{2+}$ exchanger (NCX) is the primary {C}a$^{2+}$
extrusion mechanism in cardiomyocytes. To further investigate the
role of NCX in excitation-contraction coupling and {C}a$^{2+}$ homeostasis,
we created murine models with altered expression levels of NCX. Homozygous
overexpression of NCX resulted in mild cardiac hypertrophy. Decline
of the {C}a$^{2+}$ 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 {C}a$^{2+}$-induced {C}a$^{2+}$
release. Furthermore, an increase in peak L-type {C}a$^{2+}$ current
was observed suggesting a direct influence of NCX on L-type {C}a$^{2+}$
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 {C}a$^{2+}$-handling proteins were not altered. {C}a$^{2+}$
influx in these animals is limited by a decrease of peak L-type {C}a$^{2+}$
current. An alternative {C}a$^{2+}$ efflux mechanism, presumably
the plasma membrane {C}a$^{2+}$-ATPase, is sufficient to maintain
{C}a$^{2+}$-homeostasis in the NCX knockout mice.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Pott, Christian and Goldhaber, Joshua I and Philipson, Kenneth D},
biburl = {https://www.bibsonomy.org/bibtex/21b6bf2b828e5d7a85d8499cca6168ccf/hake},
description = {The whole bibliography file I use.},
doi = {10.1016/j.bbrc.2004.08.038},
file = {Pott_2004_1336.pdf:Pott_2004_1336.pdf:PDF},
interhash = {de1024407d06bd32aceab9dcee1b965d},
intrahash = {1b6bf2b828e5d7a85d8499cca6168ccf},
journal = {Biochem. Biophys. Res. Commun.},
keywords = {15336980 Action Animals, Ca, Calcium Calcium, Cardiac, Cardiomegaly, Contraction, Disease, Electrophysiology, Energy Exchanger, Extramural, Genetic Gov't, Homozygote, Humans, Hypertrophy, Injury, Isoproterenol, Knockout, 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, Transgenic, U.S. Ventricular, lcium, to},
month = Oct,
number = 4,
pages = {1336--1340},
pii = {S0006-291X(04)01776-0},
pmid = {15336980},
timestamp = {2009-06-03T11:21:26.000+0200},
title = {Genetic manipulation of cardiac {N}a$^{+}$/{C}a$^{2+}$ exchange expression.},
url = {http://dx.doi.org/10.1016/j.bbrc.2004.08.038},
volume = 322,
year = 2004
}