Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
12-2017
Publication Source
Scientific Reports
Volume
7
Issue
1
Start Page
Article number 6687
DOI
10.1038/s41598-017-07221-9
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. © 2017 The Author(s).
Keywords
Adenosine Triphosphate, Air, Animals, Calcium Channels, Cilia, Connexins, Epithelial Cells, Mice, Inbred C57BL, Mice, Knockout, Nerve Tissue Proteins, Nose, adenosine triphosphate, air, calcium channel, CALHM1 protein, mouse, gap junction protein, nerve protein, Panx1 protein, mouse, animal, C57BL mouse, cilium, cytology, epithelium cell, knockout mouse, metabolism, nose
Recommended Citation
Workman, A. D., Carey, R. M., Chen, B., Saunders, C. J., Marambaud, P., Mitchell, C. H., Tordoff, M. G., Lee, R. J., & Cohen, N. A. (2017). CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells. Scientific Reports, 7 (1), Article number 6687-. http://dx.doi.org/10.1038/s41598-017-07221-9
Date Posted: 10 February 2023
This document has been peer reviewed.