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Multiple transport modes of the cardiac Na+/Ca2+ exchanger

Author

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  • Tong Mook Kang

    (Sungkyunkwan University School of Medicine)

  • Donald W. Hilgemann

    (University of Texas Southwestern Medical Center at Dallas)

Abstract

The cardiac Na+/Ca2+ exchanger1 (NCX1; ref. 2) is a bi-directional Ca2+ transporter that contributes to the electrical activity of the heart3,4. When, and if, Ca2+ is exported or imported depends on the Na+/Ca2+ exchange ratio5. Whereas a ratio of 3:1 (Na+:Ca2+) has been indicated by Ca2+ flux equilibrium studies6, a ratio closer to 4:1 has been indicated by exchange current reversal potentials7,8. Here we show, using an ion-selective electrode technique9 to quantify ion fluxes in giant patches10, 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.

Suggested Citation

  • Tong Mook Kang & Donald W. Hilgemann, 2004. "Multiple transport modes of the cardiac Na+/Ca2+ exchanger," Nature, Nature, vol. 427(6974), pages 544-548, February.
    • Handle: RePEc:nat:nature:v:427:y:2004:i:6974:d:10.1038_nature02271
    DOI: 10.1038/nature02271
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    Cited by:

    1. Jing Xue & Weizhong Zeng & Yan Han & Scott John & Michela Ottolia & Youxing Jiang, 2023. "Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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