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This Article Full Text Full Text (PDF) All Versions of this Article: 551/3/765    most recent jphysiol.2003.041707v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, L. Articles by Sanderson, M. J. Search for Related Content PubMed PubMed Citation Articles by Zhang, L. Articles by Sanderson, M. J.

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

Luo Zhang and Michael J. Sanderson

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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