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Swelling-activated Ca2+ Entry via TRPV4 Channel Is Defective in Cystic Fibrosis Airway Epithelia
- Source :
- Journal of Biological Chemistry. 279:54062-54068
- Publication Year :
- 2004
- Publisher :
- Elsevier BV, 2004.
-
Abstract
- The vertebrate transient receptor potential cationic channel TRPV4 has been proposed as an osmo- and mechanosensor channel. Studies using knock-out animal models have further emphasized the relevance of the TRPV4 channel in the maintenance of the internal osmotic equilibrium and mechanosensation. However, at the cellular level, there is still one important question to answer: does the TRPV4 channel generate the Ca(2+) signal in those cells undergoing a Ca(2+)-dependent regulatory volume decrease (RVD) response? RVD in human airway epithelia requires the generation of a Ca(2+) signal to activate Ca(2+)-dependent K(+) channels. The RVD response is lost in airway epithelia affected with cystic fibrosis (CF), a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator channel. We have previously shown that the defective RVD in CF epithelia is linked to the lack of swelling-dependent activation of Ca(2+)-dependent K(+) channels. In the present study, we show the expression of TRPV4 in normal human airway epithelia, where it functions as the Ca(2+) entry pathway that triggers the RVD response after hypotonic stress, as demonstrated by TRPV4 antisense experiments. However, cell swelling failed to trigger Ca(2+) entry via TRPV4 channels in CF airway epithelia, although the channel's response to a specific synthetic activator, 4 alpha-phorbol 12,13-didecanoate, was maintained. Furthermore, RVD was recovered in CF airway epithelia treated with 4 alpha-phorbol 12,13-didecanoate. Together, these results suggest that defective RVD in CF airway epithelia might be caused by the absence of a TRPV4-mediated Ca(2+) signal and the subsequent activation of Ca(2+)-dependent K(+) channels.
- Subjects :
- TRPV4
Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
TRPV Cation Channels
Biology
Transfection
Biochemistry
Cystic fibrosis
Ion Channels
Cell Line
Potassium Channels, Calcium-Activated
Transient receptor potential channel
Phorbol Esters
medicine
Humans
Cation Transport Proteins
Molecular Biology
Cell Size
Mechanosensation
Reverse Transcriptase Polymerase Chain Reaction
Activator (genetics)
Epithelial Cells
Cell Biology
medicine.disease
Potassium channel
Cystic fibrosis transmembrane conductance regulator
Cell biology
Trachea
Mutation
Immunology
biology.protein
Calcium
Signal transduction
Oligoribonucleotides, Antisense
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 279
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....b961237178dbbb2182328e90293ff281