The cardiac Na$^+$/Ca$^2+$ exchanger (NCX1; ref. 2) is a bi-directional
Ca$^2+$ transporter that contributes to the electrical activity
of the heart. When, and if, Ca$^2+$ is exported or imported depends
on the Na$^+$/Ca$^2+$ exchange ratio. Whereas a ratio of
3:1 (Na$^+$:Ca$^2+$) has been indicated by Ca$^2+$ flux
equilibrium studies, a ratio closer to 4:1 has been indicated by
exchange current reversal potentials. Here we show, using an ion-selective
electrode technique to quantify ion fluxes in giant patches, that
ion flux ratios are approximately 3.2 for maximal transport in either
direction. With Na$^+$ and Ca$^2+$ on both sides of the membrane,
net current and Ca$^2+$ flux can reverse at different membrane
potentials, and inward current can be generated in the absence of
cytoplasmic Ca$^2+$, but not Na$^+$. We propose that NCX1
can transport not only 1 Ca$^2+$ or 3 Na$^+$ ions, but also
1 Ca$^2+$ with 1 Na$^+$ ion at a low rate. Therefore, in
addition to the major 3:1 transport mode, import of 1 Na$^+$
with 1 Ca$^2+$ defines a Na$^+$-conducting mode that exports
1 Ca$^2+$, and an electroneutral Ca$^2+$ influx mode that
exports 3 Na$^+$. The two minor transport modes can potentially
determine resting free Ca$^2+$ and background inward current
in heart.
%0 Journal Article
%1 Kang_2004_544
%A Kang, Tong Mook
%A Hilgemann, Donald W
%D 2004
%J Nature
%K 14765196 Animals, Calcium, Cardiac, Cations, Cell Conductivity, Electric Exchanger, Gov't, Guinea Hamsters, Ion Line, Myocytes, Non-U.S. P.H.S., Pigs, Research Sodium, Sodium-Calcium Support, Transport, U.S.
%N 6974
%P 544--548
%R 10.1038/nature02271
%T Multiple transport modes of the cardiac Na$^+$/Ca$^2+$ exchanger.
%U http://dx.doi.org/10.1038/nature02271
%V 427
%X The cardiac Na$^+$/Ca$^2+$ exchanger (NCX1; ref. 2) is a bi-directional
Ca$^2+$ transporter that contributes to the electrical activity
of the heart. When, and if, Ca$^2+$ is exported or imported depends
on the Na$^+$/Ca$^2+$ exchange ratio. Whereas a ratio of
3:1 (Na$^+$:Ca$^2+$) has been indicated by Ca$^2+$ flux
equilibrium studies, a ratio closer to 4:1 has been indicated by
exchange current reversal potentials. Here we show, using an ion-selective
electrode technique to quantify ion fluxes in giant patches, that
ion flux ratios are approximately 3.2 for maximal transport in either
direction. With Na$^+$ and Ca$^2+$ on both sides of the membrane,
net current and Ca$^2+$ flux can reverse at different membrane
potentials, and inward current can be generated in the absence of
cytoplasmic Ca$^2+$, but not Na$^+$. We propose that NCX1
can transport not only 1 Ca$^2+$ or 3 Na$^+$ ions, but also
1 Ca$^2+$ with 1 Na$^+$ ion at a low rate. Therefore, in
addition to the major 3:1 transport mode, import of 1 Na$^+$
with 1 Ca$^2+$ defines a Na$^+$-conducting mode that exports
1 Ca$^2+$, and an electroneutral Ca$^2+$ influx mode that
exports 3 Na$^+$. The two minor transport modes can potentially
determine resting free Ca$^2+$ and background inward current
in heart.
@article{Kang_2004_544,
abstract = {The cardiac {N}a$^{+}$/{C}a$^{2+}$ exchanger (NCX1; ref. 2) is a bi-directional
{C}a$^{2+}$ transporter that contributes to the electrical activity
of the heart. When, and if, {C}a$^{2+}$ is exported or imported depends
on the {N}a$^{+}$/{C}a$^{2+}$ exchange ratio. Whereas a ratio of
3:1 ({N}a$^{+}$:{C}a$^{2+}$) has been indicated by {C}a$^{2+}$ flux
equilibrium studies, a ratio closer to 4:1 has been indicated by
exchange current reversal potentials. Here we show, using an ion-selective
electrode technique to quantify ion fluxes in giant patches, that
ion flux ratios are approximately 3.2 for maximal transport in either
direction. With {N}a$^{+}$ and {C}a$^{2+}$ on both sides of the membrane,
net current and {C}a$^{2+}$ flux can reverse at different membrane
potentials, and inward current can be generated in the absence of
cytoplasmic {C}a$^{2+}$, but not {N}a$^{+}$. We propose that NCX1
can transport not only 1 {C}a$^{2+}$ or 3 {N}a$^{+}$ ions, but also
1 {C}a$^{2+}$ with 1 {N}a$^{+}$ ion at a low rate. Therefore, in
addition to the major 3:1 transport mode, import of 1 {N}a$^{+}$
with 1 {C}a$^{2+}$ defines a {N}a$^{+}$-conducting mode that exports
1 {C}a$^{2+}$, and an electroneutral {C}a$^{2+}$ influx mode that
exports 3 {N}a$^{+}$. The two minor transport modes can potentially
determine resting free {C}a$^{2+}$ and background inward current
in heart.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Kang, Tong Mook and Hilgemann, Donald W},
biburl = {https://www.bibsonomy.org/bibtex/256e3ad167854e18351aa8a48d44fb922/hake},
description = {The whole bibliography file I use.},
doi = {10.1038/nature02271},
file = {Kang_2004_544.pdf:Kang_2004_544.pdf:PDF},
interhash = {9e11bf05341d7a7dba10868ecc4a08e3},
intrahash = {56e3ad167854e18351aa8a48d44fb922},
journal = {Nature},
key = 164,
keywords = {14765196 Animals, Calcium, Cardiac, Cations, Cell Conductivity, Electric Exchanger, Gov't, Guinea Hamsters, Ion Line, Myocytes, Non-U.S. P.H.S., Pigs, Research Sodium, Sodium-Calcium Support, Transport, U.S.},
month = Feb,
number = 6974,
pages = {544--548},
pii = {nature02271},
pmid = {14765196},
timestamp = {2009-06-03T11:21:17.000+0200},
title = {Multiple transport modes of the cardiac {N}a$^{+}$/{C}a$^{2+}$ exchanger.},
url = {http://dx.doi.org/10.1038/nature02271},
volume = 427,
year = 2004
}