Intracellular Na$^+$ (Na$^+$i) is regulated in cardiac
myocytes by a balance of Na$^+$ influx and efflux mechanisms.
In the normal cell there is a large steady state electrochemical
gradient favoring Na$^+$ influx. This potential energy is used
by numerous transport mechanisms, including Na$^+$ channels and
transporters which couple Na$^+$ influx to either co- or counter-transport
of other ions and solutes. Six sarcolemmal Na$^+$ influx pathways
are discussed in relatively quantitative terms: Na$^+$ channels,
Na$^+$/Ca$^2+$ exchange, Na$^+$/H$^+$ exchange, Na$^+$/Mg2+
exchange, Na$^+$/HCO3- cotransport and Na$^+$/K$^+$/2Cl$^-$
cotransport. Under normal conditions Na$^+$/Ca$^2+$ exchange
and Na$^+$ channels are the dominant Na$^+$ influx pathways,
but other transporters may become increasingly important during altered
conditions (e.g. acidosis or cell volume stress). Mitochondria also
exhibit Na$^+$/Ca$^2+$ antiporter and Na$^+$/H$^+$
exchange activity that are important in mitochondrial function. These
coupled fluxes of Na$^+$ with Ca$^2+$, H$^+$ and HCO3-
make the detailed understanding of Na$^+$i regulation pivotal
to the understanding of both cardiac excitation-contraction coupling
and pH regulation. The Na$^+$/K$^+$-ATPase is the main route
for Na$^+$ extrusion from cells and Na$^+$i is a primary
regulator under physiological conditions. Na$^+$i is higher
in rat than rabbit ventricular myocytes and the reason appears to
be higher Na$^+$ influx in rat with a consequent rise in Na$^+$/K$^+$-ATPase
activity (rather than lower Na$^+$/K$^+$-ATPase function
in rat). This has direct functional consequences. There may also
be subcellular Na$^+$i gradients locally in ventricular myocytes
and this may also have important functional implications. Thus, the
balance of Na$^+$ fluxes in heart cells may be complex, but myocyte
Na$^+$ regulation is functionally important and merits focused
attention as in this issue.
%0 Journal Article
%1 Bers_2003_897
%A Bers, Donald M
%A Barry, William H
%A Despa, Sanda
%D 2003
%J Cardiovasc. Res.
%K 12650864 ATPase, Active, Adaptation, Animals, Antiporter, Biological Biological, Calcium, Capacitance, Cardiac, Cell Cells, Comparative Computer Cultured, Diffusion, Distribution, Electric Exchanger, Gov't, H.S., Heart Intracellular Membrane Models, Muscle Myocytes, Non-U.S. P., P.H.S., Physiological, Potentials, Rabbits, Rats, Research Sarcolemma, Simulation, Size, Sodium, Sodium-Calcium Sodium-Hydrogen Space, Study, Support, Tissue Transport, U.S. Ventricles, {N}a$^{+}$-{K}$^{+}$-Exchanging
%N 4
%P 897--912
%T Intracellular Na$^+$ regulation in cardiac myocytes.
%U http://dx.doi.org/10.1016/S0008-6363(02)00656-9
%V 57
%X Intracellular Na$^+$ (Na$^+$i) is regulated in cardiac
myocytes by a balance of Na$^+$ influx and efflux mechanisms.
In the normal cell there is a large steady state electrochemical
gradient favoring Na$^+$ influx. This potential energy is used
by numerous transport mechanisms, including Na$^+$ channels and
transporters which couple Na$^+$ influx to either co- or counter-transport
of other ions and solutes. Six sarcolemmal Na$^+$ influx pathways
are discussed in relatively quantitative terms: Na$^+$ channels,
Na$^+$/Ca$^2+$ exchange, Na$^+$/H$^+$ exchange, Na$^+$/Mg2+
exchange, Na$^+$/HCO3- cotransport and Na$^+$/K$^+$/2Cl$^-$
cotransport. Under normal conditions Na$^+$/Ca$^2+$ exchange
and Na$^+$ channels are the dominant Na$^+$ influx pathways,
but other transporters may become increasingly important during altered
conditions (e.g. acidosis or cell volume stress). Mitochondria also
exhibit Na$^+$/Ca$^2+$ antiporter and Na$^+$/H$^+$
exchange activity that are important in mitochondrial function. These
coupled fluxes of Na$^+$ with Ca$^2+$, H$^+$ and HCO3-
make the detailed understanding of Na$^+$i regulation pivotal
to the understanding of both cardiac excitation-contraction coupling
and pH regulation. The Na$^+$/K$^+$-ATPase is the main route
for Na$^+$ extrusion from cells and Na$^+$i is a primary
regulator under physiological conditions. Na$^+$i is higher
in rat than rabbit ventricular myocytes and the reason appears to
be higher Na$^+$ influx in rat with a consequent rise in Na$^+$/K$^+$-ATPase
activity (rather than lower Na$^+$/K$^+$-ATPase function
in rat). This has direct functional consequences. There may also
be subcellular Na$^+$i gradients locally in ventricular myocytes
and this may also have important functional implications. Thus, the
balance of Na$^+$ fluxes in heart cells may be complex, but myocyte
Na$^+$ regulation is functionally important and merits focused
attention as in this issue.
@article{Bers_2003_897,
abstract = {Intracellular [{N}a$^{+}$] ([{N}a$^{+}$]i) is regulated in cardiac
myocytes by a balance of {N}a$^{+}$ influx and efflux mechanisms.
In the normal cell there is a large steady state electrochemical
gradient favoring {N}a$^{+}$ influx. This potential energy is used
by numerous transport mechanisms, including {N}a$^{+}$ channels and
transporters which couple {N}a$^{+}$ influx to either co- or counter-transport
of other ions and solutes. Six sarcolemmal {N}a$^{+}$ influx pathways
are discussed in relatively quantitative terms: {N}a$^{+}$ channels,
{N}a$^{+}$/{C}a$^{2+}$ exchange, {N}a$^{+}$/{H}$^+$ exchange, {N}a$^{+}$/Mg2+
exchange, {N}a$^{+}$/{HCO}3- cotransport and {N}a$^{+}$/{K}$^{+}$/2{C}l$^{-}$
cotransport. Under normal conditions {N}a$^{+}$/{C}a$^{2+}$ exchange
and {N}a$^{+}$ channels are the dominant {N}a$^{+}$ influx pathways,
but other transporters may become increasingly important during altered
conditions (e.g. acidosis or cell volume stress). Mitochondria also
exhibit {N}a$^{+}$/{C}a$^{2+}$ antiporter and {N}a$^{+}$/{H}$^+$
exchange activity that are important in mitochondrial function. These
coupled fluxes of {N}a$^{+}$ with {C}a$^{2+}$, {H}$^+$ and {HCO}3-
make the detailed understanding of [{N}a$^{+}$]i regulation pivotal
to the understanding of both cardiac excitation-contraction coupling
and pH regulation. The {N}a$^{+}$/{K}$^{+}$-ATPase is the main route
for {N}a$^{+}$ extrusion from cells and [{N}a$^{+}$]i is a primary
regulator under physiological conditions. [{N}a$^{+}$]i is higher
in rat than rabbit ventricular myocytes and the reason appears to
be higher {N}a$^{+}$ influx in rat with a consequent rise in {N}a$^{+}$/{K}$^{+}$-ATPase
activity (rather than lower {N}a$^{+}$/{K}$^{+}$-ATPase function
in rat). This has direct functional consequences. There may also
be subcellular [{N}a$^{+}$]i gradients locally in ventricular myocytes
and this may also have important functional implications. Thus, the
balance of {N}a$^{+}$ fluxes in heart cells may be complex, but myocyte
{N}a$^{+}$ regulation is functionally important and merits focused
attention as in this issue.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Bers, Donald M and Barry, William H and Despa, Sanda},
biburl = {https://www.bibsonomy.org/bibtex/217f6677202e1b77b574c3a5f7e4ce423/hake},
description = {The whole bibliography file I use.},
file = {Bers_2003_897.pdf:Bers_2003_897.pdf:PDF},
interhash = {6eff74d0e5930bf596c335de15d9e40b},
intrahash = {17f6677202e1b77b574c3a5f7e4ce423},
journal = {Cardiovasc. Res.},
key = 69,
keywords = {12650864 ATPase, Active, Adaptation, Animals, Antiporter, Biological Biological, Calcium, Capacitance, Cardiac, Cell Cells, Comparative Computer Cultured, Diffusion, Distribution, Electric Exchanger, Gov't, H.S., Heart Intracellular Membrane Models, Muscle Myocytes, Non-U.S. P., P.H.S., Physiological, Potentials, Rabbits, Rats, Research Sarcolemma, Simulation, Size, Sodium, Sodium-Calcium Sodium-Hydrogen Space, Study, Support, Tissue Transport, U.S. Ventricles, {N}a$^{+}$-{K}$^{+}$-Exchanging},
month = Mar,
number = 4,
pages = {897--912},
pii = {S0008636302006569},
pmid = {12650864},
timestamp = {2009-06-03T11:21:03.000+0200},
title = {Intracellular {N}a$^{+}$ regulation in cardiac myocytes.},
url = {http://dx.doi.org/10.1016/S0008-6363(02)00656-9},
volume = 57,
year = 2003
}