TY - JOUR
T1 - Multiple transport modes of the cardiac Na+/Ca2+ exchanger
AU - Kang, Tong Mook
AU - Hilgemann, Donald W.
N1 - Funding Information:
Acknowledgements We thank S. Feng and P. Foley for technical assistance; K. Philipson for providing the BHK cell line; L. Hrysko for defining NCX1 I–Vs with organic NCX1 inhibitors; and A. Ferguson and L. DeFelice for critical comments on the manuscript. This work was supported by an NIH grant to D.W.H. and a Samsung Biomedical Research Institute grant to T.M.K.
Funding Information:
Acknowledgements We are grateful to T. Vision for help with bioinformatics, R. Wallin for technical assistance with the VKOR assay, and S. Makarov for assistance with quantitative PCR. For editorial assistance we thank L. Gabiger. This work was supported by grants from the NIH.
PY - 2004/2/5
Y1 - 2004/2/5
N2 - The cardiac Na+/Ca2+ exchanger (NCX1; ref. 2) is a bi-directional Ca2+ transporter that contributes to the electrical activity of the heart. When, and if, Ca2+ is exported or imported depends on the Na+/Ca2+ exchange ratio. Whereas a ratio of 3:1 (Na+:Ca2+) has been indicated by Ca2+ 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 Ca2+ on both sides of the membrane, net current and Ca2+ flux can reverse at different membrane potentials, and inward current can be generated in the absence of cytoplasmic Ca2+, but not Na+. We propose that NCX1 can transport not only 1 Ca2+ or 3 Na+ ions, but also 1 Ca2+ with 1 Na+ ion at a low rate. Therefore, in addition to the major 3:1 transport mode, import of 1 Na+ with 1 Ca2+ defines a Na+-conducting mode that exports 1 Ca2+, and an electroneutral Ca2+ influx mode that exports 3 Na+. The two minor transport modes can potentially determine resting free Ca2+ and background inward current in heart.
AB - The cardiac Na+/Ca2+ exchanger (NCX1; ref. 2) is a bi-directional Ca2+ transporter that contributes to the electrical activity of the heart. When, and if, Ca2+ is exported or imported depends on the Na+/Ca2+ exchange ratio. Whereas a ratio of 3:1 (Na+:Ca2+) has been indicated by Ca2+ 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 Ca2+ on both sides of the membrane, net current and Ca2+ flux can reverse at different membrane potentials, and inward current can be generated in the absence of cytoplasmic Ca2+, but not Na+. We propose that NCX1 can transport not only 1 Ca2+ or 3 Na+ ions, but also 1 Ca2+ with 1 Na+ ion at a low rate. Therefore, in addition to the major 3:1 transport mode, import of 1 Na+ with 1 Ca2+ defines a Na+-conducting mode that exports 1 Ca2+, and an electroneutral Ca2+ influx mode that exports 3 Na+. The two minor transport modes can potentially determine resting free Ca2+ and background inward current in heart.
UR - http://www.scopus.com/inward/record.url?scp=1142274551&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1142274551&partnerID=8YFLogxK
U2 - 10.1038/nature02271
DO - 10.1038/nature02271
M3 - Article
C2 - 14765196
AN - SCOPUS:1142274551
SN - 0028-0836
VL - 427
SP - 544
EP - 548
JO - Nature
JF - Nature
IS - 6974
ER -