Article,
Multiple transport modes of the cardiac Na$^+$/Ca$^2+$ exchanger.
Nature, 427 (6974): 544--548 (February 2004)
DOI: 10.1038/nature02271
Abstract
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.
Tags
- 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.
