CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells

Abstract Mechanical stimulation of airway epithelial cells causes apical release of ATP, which increases ciliary beat frequency (CBF) and speeds up mucociliary clearance. The mechanisms responsible for this ATP release are poorly understood. CALHM1, a transmembrane protein with shared structural fea...

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Autores principales:	Alan D. Workman, Ryan M. Carey, Bei Chen, Cecil J. Saunders, Philippe Marambaud, Claire H. Mitchell, Michael G. Tordoff, Robert J. Lee, Noam A. Cohen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c82aa564940a442ca73ece8582700867
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spelling	oai:doaj.org-article:c82aa564940a442ca73ece85827008672021-12-02T16:06:14ZCALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells10.1038/s41598-017-07221-92045-2322https://doaj.org/article/c82aa564940a442ca73ece85827008672017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07221-9https://doaj.org/toc/2045-2322Abstract Mechanical stimulation of airway epithelial cells causes apical release of ATP, which increases ciliary beat frequency (CBF) and speeds up mucociliary clearance. The mechanisms responsible for this ATP release are poorly understood. CALHM1, a transmembrane protein with shared structural features to connexins and pannexins, has been implicated in ATP release from taste buds, but it has not been evaluated for a functional role in the airway. In the present study, Calhm1 knockout, Panx1 knockout, and wild-type mouse nasal septal epithelial cells were grown at an air-liquid interface (ALI) and subjected to light mechanical stimulation from an air puff. Apical ATP release was attenuated in Calhm1 knockout cultures following mechanical stimulation at a pressure of 55 mmHg for 50 milliseconds (p < 0.05). Addition of carbenoxolone, a PANX1 channel blocker, completely abolished ATP release in Calhm1 knockout cultures but not in wild type or Panx1 knockout cultures. An increase in CBF was observed in wild-type ALIs following mechanical stimulation, and this increase was significantly lower (p < 0.01) in Calhm1 knockout cultures. These results demonstrate that CALHM1 plays a newly defined role, complementary to PANX1, in ATP release and downstream CBF modulation following a mechanical stimulus in airway epithelial cells.Alan D. WorkmanRyan M. CareyBei ChenCecil J. SaundersPhilippe MarambaudClaire H. MitchellMichael G. TordoffRobert J. LeeNoam A. CohenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alan D. Workman Ryan M. Carey Bei Chen Cecil J. Saunders Philippe Marambaud Claire H. Mitchell Michael G. Tordoff Robert J. Lee Noam A. Cohen CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells
description	Abstract Mechanical stimulation of airway epithelial cells causes apical release of ATP, which increases ciliary beat frequency (CBF) and speeds up mucociliary clearance. The mechanisms responsible for this ATP release are poorly understood. CALHM1, a transmembrane protein with shared structural features to connexins and pannexins, has been implicated in ATP release from taste buds, but it has not been evaluated for a functional role in the airway. In the present study, Calhm1 knockout, Panx1 knockout, and wild-type mouse nasal septal epithelial cells were grown at an air-liquid interface (ALI) and subjected to light mechanical stimulation from an air puff. Apical ATP release was attenuated in Calhm1 knockout cultures following mechanical stimulation at a pressure of 55 mmHg for 50 milliseconds (p < 0.05). Addition of carbenoxolone, a PANX1 channel blocker, completely abolished ATP release in Calhm1 knockout cultures but not in wild type or Panx1 knockout cultures. An increase in CBF was observed in wild-type ALIs following mechanical stimulation, and this increase was significantly lower (p < 0.01) in Calhm1 knockout cultures. These results demonstrate that CALHM1 plays a newly defined role, complementary to PANX1, in ATP release and downstream CBF modulation following a mechanical stimulus in airway epithelial cells.
format	article
author	Alan D. Workman Ryan M. Carey Bei Chen Cecil J. Saunders Philippe Marambaud Claire H. Mitchell Michael G. Tordoff Robert J. Lee Noam A. Cohen
author_facet	Alan D. Workman Ryan M. Carey Bei Chen Cecil J. Saunders Philippe Marambaud Claire H. Mitchell Michael G. Tordoff Robert J. Lee Noam A. Cohen
author_sort	Alan D. Workman
title	CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells
title_short	CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells
title_full	CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells
title_fullStr	CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells
title_full_unstemmed	CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells
title_sort	calhm1-mediated atp release and ciliary beat frequency modulation in nasal epithelial cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c82aa564940a442ca73ece8582700867
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CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells

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