Extracellular sodium regulates airway ciliary motility by inhibiting a P2X receptor.
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 airways. 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 (ATP0), which acts by releasing calcium ions from internal stores and by activating calcium influx. Here we show that, in airway ciliated cells, extracellular sodium ions (Na+(0)) specifically and competitively inhibit an ATP0-gated channel that is permeable to calcium ions, and thereby attenuate ATP0-induced ciliary motility. Our finding points to a physiological role for Na+(0) 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.
Ma
W
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Department of Chemistry, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Korngreen
A
A
Uzlaner
N
N
Priel
Z
Z
Silberberg
S D
SD
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002923:Cilia / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D015640:Ion Channel Gating; D009297:Nasal Mucosa / Q000166:cytology; D010766:Phosphorylation; D058919:Purinergic P2 Receptor Antagonists; D011817:Rabbits; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012137:Respiratory System / Q000166:cytology; D012964:Sodium / Q000494:pharmacology*
D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D012964:Sodium; D002118:Calcium