Title

The role of cGMP in the regulation of rabbit airway ciliary beat frequency

UMMS Affiliation

Department of Physiology

Publication Date

6-24-2003

Document Type

Article

Subjects

Animals; Buffers; 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

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: J Physiol. 2003 Sep 15;551(Pt 3):765-76. Epub 2003 Jun 20. Link to article on publisher's site

DOI of Published Version

10.1113/jphysiol.2003.041707

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of physiology

PubMed ID

12819300