The role of cGMP in the regulation of rabbit airway ciliary beat frequency
UMass Chan Affiliations
Department of PhysiologyDocument Type
Journal ArticlePublication Date
2003-06-24Keywords
AnimalsBuffers
Calcium
Calcium Signaling
Carbazoles
Cells, Cultured
Cilia
Cyclic GMP
Cyclic GMP-Dependent Protein Kinases
Dose-Response Relationship, Drug
Enzyme Inhibitors
Indoles
Ionomycin
Ionophores
Rabbits
Respiratory Mucosa
Trachea
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The involvement of cyclic guanosine 3',5'-monophosphate (cGMP) and cGMP-dependent protein kinase (PKG) and their interaction with the Ca2+-dependent mechanisms in the regulation of ciliary activity are not well understood. To investigate how cGMP regulates ciliary activity, changes in ciliary beat frequency (CBF) and intracellular calcium concentration ([Ca2+]i) of rabbit tracheal ciliated cells in response to 8-bromo-cGMP (Br-cGMP) were simultaneously quantified using digital, high-speed phase-contrast and fluorescence imaging. Br-cGMP induced a response in ciliary activity that could be separated into two parts. Firstly, Br-cGMP induced a concentration-dependent increase in the basal CBF that occurred without increasing the [Ca2+]i. This response was not affected by excessively buffering the [Ca2+]i with BAPTA but was abolished by KT5823, a PKG inhibitor. Secondly, Br-cGMP induced a series of transient increases in CBF that were superimposed on the sustained increases in CBF. These transient increases in CBF correlated with the stimulation of a series of transient increases in [Ca2+]i and were abolished by BAPTA, but were unaffected by KT5823. The magnitude of the transient increases in CBF and [Ca2+]i were not dependent on the concentration of Br-cGMP. The Ca2+-dependent changes in CBF induced by ionomycin or ATP were not affected by KT5823. From these results, we propose that cGMP increases CBF in two ways: firstly through a Ca2+-independent mechanism involving PKG, and secondly through a Ca2+-dependent mechanism following the stimulation of changes in [Ca2+]i. In addition, we suggest that the Ca2+-dependent stimulation of rabbit airway ciliary activity does not initially require PKG activation.Source
J Physiol. 2003 Sep 15;551(Pt 3):765-76. Epub 2003 Jun 20. Link to article on publisher's site
DOI
10.1113/jphysiol.2003.041707Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38621PubMed ID
12819300Related Resources
ae974a485f413a2113503eed53cd6c53
10.1113/jphysiol.2003.041707