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

L Zhang, MJ Sanderson - The Journal of physiology, 2003 - Wiley Online Library
L Zhang, MJ Sanderson
The Journal of physiology, 2003Wiley Online Library
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 …
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.
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