Localized cytosolic alkalization and its functional impact in ciliary cells

Using confocal microscopy we demonstrate that ciliary cells from airway epithelium maintain two qualitatively distinct cytosolic regions in terms of pH regulation. While the bulk of the cytosol is stringently buffered and is virtually insensitive to changes in extracellular pH (pHo), the values of c...

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Bibliographic Details
Published in:Biochimica et biophysica acta 2008-06, Vol.1783 (6), p.1102-1110
Main Authors: Lemberskiy-Kuzin, Liubov, Fainshtein, Michal, Fridman, Polina, Passwell, Elena, Braiman, Alex, Priel, Zvi
Format: Article
Language:English
Subjects:
Acid-base balance
Airway epithelium
Ammonia
Ammonium Chloride - pharmacology
Animals
Calcium - metabolism
Calcium Signaling
Calmodulin - metabolism
Cells, Cultured
Cilia - drug effects
Cilia - physiology
Ciliary beating
Cyclic AMP - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
Cytosol - metabolism
Cytosolic gradient
Epithelial Cells - metabolism
Hydrogen-Ion Concentration
Microscopy, Confocal
Mucociliary
Rabbits
Respiratory Mucosa - cytology
Swine
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Summary:Using confocal microscopy we demonstrate that ciliary cells from airway epithelium maintain two qualitatively distinct cytosolic regions in terms of pH regulation. While the bulk of the cytosol is stringently buffered and is virtually insensitive to changes in extracellular pH (pHo), the values of cytosolic pH in the vicinity of the ciliary membrane is largely determined by pHo. Variation of pHo from 6.2 up to 8.5 failed to affect ciliary beat frequency (CBF). Application of NH4Cl induced profound localized alkalization near cilia, which did not depress ciliary activity, but resulted in strong and prolonged enhancement of CBF. Calmodulin and protein kinase A (PKA) functionality was essential for the alkalization-induced CBF enhancement. We suggest that the ability of airway epithelium to sustain unusually strong but localized cytosolic alkalization near cilia facilitates CBF enhancement through altering the binding constants of Ca2+ to calmodulin and promotion of Ca2+–calmodulin complex formation. The NH4Cl-induced elevations in cytosolic pH and Ca2+ concentration act synergistically to activate calmodulin-dependent processes, cAMP pathway, and, thereby, stimulate CBF.
ISSN:0167-4889
0006-3002
1879-2596
DOI:10.1016/j.bbamcr.2008.02.005