Cardiac sarcolemmal Na$^+$--Ca$^2+$ exchange is a central
component of Ca$^2+$ signaling essential for Ca$^2+$ extrusion
and contributing to a variable degree to the development of the systolic
Ca$^2+$ transient. Reports on differential gene expression of
Na$^+$--Ca$^2+$ exchange in cardiac disease and the regulation
of its thermodynamic equilibrium depending on intracellular gradients
of ion concentrations between subcellular compartments have recently
put a new complexion on Na$^+$--Ca$^2+$ exchange and its
implications for excitation-contraction (E-C) coupling. Heart failure
models and genetic approaches to regulate expression of the Na$^+$--Ca$^2+$
exchanger have improved our knowledge of exchanger function. Modest
overexpression of the Na$^+$--Ca$^2+$ exchanger in heterozygous
transgenic mice had minimal effects on E-C coupling and cardiac function.
However, higher levels of Na$^+$--Ca$^2+$ exchange expression
in homozygotes led to pathological hypertrophy and failure with an
increased interaction between the L-type Ca$^2+$ current and
Na$^+$--Ca$^2+$ exchange and reduced E-C coupling gain. These
results suggested that the Na$^+$--Ca$^2+$ exchanger is capable
of modulating sarcoplasmic Ca$^2+$ handling and at high expression
levels may interact with the gating kinetics of the L-type Ca$^2+$
current by means of regulating subsarcolemmal Ca$^2+$ levels.
Despite being a central component in the regulation of cardiac E-C
coupling, a newly generated mouse model with cardiac-specific conditional
knock-out of the Na$^+$--Ca$^2+$ exchanger is viable with
unchanged Ca$^2+$ dynamics in adult ventricular myocytes. Cardiac
myocytes adapt well to knock-out of the exchanger, apparently by
reducing transsarcolemmal fluxes of Ca$^2+$ and increasing E-C
coupling gain possibly mediated by changes in submembrane Ca$^2+$
levels. For E-C coupling in the murine model, which relies primarily
on sarcoplasmic Ca$^2+$ regulation, this led to the suggestion
that the role of Na$^+$--Ca$^2+$ exchange should be thought
of as a Ca$^2+$ buffering function and not as a major Ca$^2+$
transporter in competition with the sarcoplasmic reticulum.
%0 Journal Article
%1 Reut_2005_198
%A Reuter, Hannes
%A Pott, Christian
%A Goldhaber, Joshua I
%A Henderson, Scott A
%A Philipson, Kenneth D
%A Schwinger, Robert H G
%D 2005
%J Cardiovasc. Res.
%K 15935336 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 2
%P 198--207
%R 10.1016/j.cardiores.2005.04.031
%T Na$^+$--Ca$^2+$ exchange in the regulation of cardiac excitation-contraction
coupling.
%U http://dx.doi.org/10.1016/j.cardiores.2005.04.031
%V 67
%X Cardiac sarcolemmal Na$^+$--Ca$^2+$ exchange is a central
component of Ca$^2+$ signaling essential for Ca$^2+$ extrusion
and contributing to a variable degree to the development of the systolic
Ca$^2+$ transient. Reports on differential gene expression of
Na$^+$--Ca$^2+$ exchange in cardiac disease and the regulation
of its thermodynamic equilibrium depending on intracellular gradients
of ion concentrations between subcellular compartments have recently
put a new complexion on Na$^+$--Ca$^2+$ exchange and its
implications for excitation-contraction (E-C) coupling. Heart failure
models and genetic approaches to regulate expression of the Na$^+$--Ca$^2+$
exchanger have improved our knowledge of exchanger function. Modest
overexpression of the Na$^+$--Ca$^2+$ exchanger in heterozygous
transgenic mice had minimal effects on E-C coupling and cardiac function.
However, higher levels of Na$^+$--Ca$^2+$ exchange expression
in homozygotes led to pathological hypertrophy and failure with an
increased interaction between the L-type Ca$^2+$ current and
Na$^+$--Ca$^2+$ exchange and reduced E-C coupling gain. These
results suggested that the Na$^+$--Ca$^2+$ exchanger is capable
of modulating sarcoplasmic Ca$^2+$ handling and at high expression
levels may interact with the gating kinetics of the L-type Ca$^2+$
current by means of regulating subsarcolemmal Ca$^2+$ levels.
Despite being a central component in the regulation of cardiac E-C
coupling, a newly generated mouse model with cardiac-specific conditional
knock-out of the Na$^+$--Ca$^2+$ exchanger is viable with
unchanged Ca$^2+$ dynamics in adult ventricular myocytes. Cardiac
myocytes adapt well to knock-out of the exchanger, apparently by
reducing transsarcolemmal fluxes of Ca$^2+$ and increasing E-C
coupling gain possibly mediated by changes in submembrane Ca$^2+$
levels. For E-C coupling in the murine model, which relies primarily
on sarcoplasmic Ca$^2+$ regulation, this led to the suggestion
that the role of Na$^+$--Ca$^2+$ exchange should be thought
of as a Ca$^2+$ buffering function and not as a major Ca$^2+$
transporter in competition with the sarcoplasmic reticulum.
@article{Reut_2005_198,
abstract = {Cardiac sarcolemmal {N}a$^{+}$--{C}a$^{2+}$ exchange is a central
component of {C}a$^{2+}$ signaling essential for {C}a$^{2+}$ extrusion
and contributing to a variable degree to the development of the systolic
{C}a$^{2+}$ transient. Reports on differential gene expression of
{N}a$^{+}$--{C}a$^{2+}$ exchange in cardiac disease and the regulation
of its thermodynamic equilibrium depending on intracellular gradients
of ion concentrations between subcellular compartments have recently
put a new complexion on {N}a$^{+}$--{C}a$^{2+}$ exchange and its
implications for excitation-contraction (E-C) coupling. Heart failure
models and genetic approaches to regulate expression of the {N}a$^{+}$--{C}a$^{2+}$
exchanger have improved our knowledge of exchanger function. Modest
overexpression of the {N}a$^{+}$--{C}a$^{2+}$ exchanger in heterozygous
transgenic mice had minimal effects on E-C coupling and cardiac function.
However, higher levels of {N}a$^{+}$--{C}a$^{2+}$ exchange expression
in homozygotes led to pathological hypertrophy and failure with an
increased interaction between the L-type {C}a$^{2+}$ current and
{N}a$^{+}$--{C}a$^{2+}$ exchange and reduced E-C coupling gain. These
results suggested that the {N}a$^{+}$--{C}a$^{2+}$ exchanger is capable
of modulating sarcoplasmic {C}a$^{2+}$ handling and at high expression
levels may interact with the gating kinetics of the L-type {C}a$^{2+}$
current by means of regulating subsarcolemmal {C}a$^{2+}$ levels.
Despite being a central component in the regulation of cardiac E-C
coupling, a newly generated mouse model with cardiac-specific conditional
knock-out of the {N}a$^{+}$--{C}a$^{2+}$ exchanger is viable with
unchanged {C}a$^{2+}$ dynamics in adult ventricular myocytes. Cardiac
myocytes adapt well to knock-out of the exchanger, apparently by
reducing transsarcolemmal fluxes of {C}a$^{2+}$ and increasing E-C
coupling gain possibly mediated by changes in submembrane {C}a$^{2+}$
levels. For E-C coupling in the murine model, which relies primarily
on sarcoplasmic {C}a$^{2+}$ regulation, this led to the suggestion
that the role of {N}a$^{+}$--{C}a$^{2+}$ exchange should be thought
of as a {C}a$^{2+}$ buffering function and not as a major {C}a$^{2+}$
transporter in competition with the sarcoplasmic reticulum.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Reuter, Hannes and Pott, Christian and Goldhaber, Joshua I and Henderson, Scott A and Philipson, Kenneth D and Schwinger, Robert H G},
biburl = {https://www.bibsonomy.org/bibtex/294b78f30bd1e5f07859c2ab752ba1b2a/hake},
description = {The whole bibliography file I use.},
doi = {10.1016/j.cardiores.2005.04.031},
file = {Reut_2005_198.pdf:Reut_2005_198.pdf:PDF},
interhash = {a9615b4b4ce527b28daabc6157d31371},
intrahash = {94b78f30bd1e5f07859c2ab752ba1b2a},
journal = {Cardiovasc. Res.},
keywords = {15935336 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 = Aug,
number = 2,
pages = {198--207},
pii = {S0008-6363(05)00221-X},
pmid = {15935336},
timestamp = {2009-06-03T11:21:26.000+0200},
title = {{N}a$^{+}$--{C}a$^{2+}$ exchange in the regulation of cardiac excitation-contraction
coupling.},
url = {http://dx.doi.org/10.1016/j.cardiores.2005.04.031},
volume = 67,
year = 2005
}