The role of cGMP in the regulation of rabbit airway ciliary beat frequency
Department of Physiology
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
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
J Physiol. 2003 Sep 15;551(Pt 3):765-76. Epub 2003 Jun 20. Link to article on publisher's site
The Journal of physiology
Zhang, Luo and Sanderson, Michael J., "The role of cGMP in the regulation of rabbit airway ciliary beat frequency" (2003). Open Access Articles. 1483.