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Extracellular sodium regulates airway ciliary motility by inhibiting a P2X receptor

Nature volume 400, pages 894–897 (1999)Cite this article

Abstract

The mucociliary system is responsible for clearing inhaled particles and pathogens from the airways. This important task is performed by the beating of cilia and the consequent movement of mucus from the lungs to the upper airways1,2. Because ciliary motility is enhanced by elevated intracellular calcium concentrations, inhibition of calcium influx could lead to disease by jeopardizing mucociliary clearance. Several hormones and neurotransmitters stimulate ciliary motility, one of the most potent of which is extracellular ATP (ATPo)1, which acts by releasing calcium ions from internal stores and by activating calcium influx3,4,5. Here we show that, in airway ciliated cells, extracellular sodium ions (Nao+) specifically and competitively inhibit an ATPo-gated channel that is permeable to calcium ions, and thereby attenuate ATPo-induced ciliary motility. Our finding points to a physiological role for Nao+ in ciliary function, and indicates that mucociliary clearance might be improved in respiratory disorders such as chronic bronchitis and cystic fibrosis by decreasing the sodium concentration of the airway surface fluid in which the cilia are bathed.

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Figure 1: Nao+ competitively inhibits the current activated by ATPo.
Figure 2: Nao+ directly and specifically inhibits P2Xcilia channels.
Figure 3: Nao+ attenuates ATPo-induced ciliary activity by inhibiting P2Xcilia channels.

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Acknowledgements

We thank G. David, Z. Gill, M. J. Gutnick, K. L. Magleby, B. Sakmann and D. S. Weiss for comments and suggestions on the manuscript, and Y. Rodrig for providing freshly dissociated pig airway ciliated cells. This work was supported by The Israel Science Foundation founded by the Israel Academy of Sciences and Humanities — Dorot Science Foundation.

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Author notes

  1. Alon Korngreen

    Present address: Max-Planck Institut für medizinische Forschung Abteilung Zellphysiologie, Jahnstrasse 29, D-69120, Heidelberg, Germany

  2. Weiyuan Ma, Alon Korngreen and Natalya Uzlaner: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Chemistry, Ben-Gurion University of the Negev, 84105, Beer-Sheva, Israel

    Weiyuan Ma, Alon Korngreen, Natalya Uzlaner & Zvi Priel

  2. Department of Life Sciences and The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, 84105, Beer-Sheva, Israel

    Shai D. Silberberg

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  1. Weiyuan Ma
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  5. Shai D. Silberberg
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Correspondence to Shai D. Silberberg.

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Ma, W., Korngreen, A., Uzlaner, N. et al. Extracellular sodium regulates airway ciliary motility by inhibiting a P2X receptor. Nature 400, 894–897 (1999). https://doi.org/10.1038/23743

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