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Modulation of Ca2-Activated Cl−Secretion by Basolateral KChannels in Human Normal and Cystic Fibrosis Airway Epithelia
- Source :
- Pediatric Research (Ovid); April 2003, Vol. 53 Issue: 4 p608-618, 11p
- Publication Year :
- 2003
-
Abstract
- Human airway epithelia express Ca2-activated Cl−channels (CaCC) that are activated by extracellular nucleotides (ATP and UTP). CaCC is preserved and seems to be up-regulated in the airways of cystic fibrosis (CF) patients. In the present study, we examined the role of basolateral Kchannels in CaCC-mediated Cl−secretion in native nasal tissues from normal individuals and CF patients by measuring ion transport in perfused micro Ussing chambers. In the presence of amiloride, UTP-mediated peak secretory responses were increased in CF compared with normal nasal tissues. Activation of the cAMP pathway further increased CaCC-mediated secretion in CF but not in normal nasal mucosa. CaCC-dependent ion transport was inhibited by the chromanol 293B, an inhibitor of cAMP-activated hKvLQT1 Kchannels, and by clotrimazole, an inhibitor of Ca2-activated hSK4 Kchannels. The Kchannel opener 1-ethyl-2-benzimidazolinone further increased CaCC-mediated Cl−secretion in normal and CF tissues. Expression of hSK4 as well as hCACC-2 and hCACC-3 but not hCACC-1 was demonstrated by reverse transcriptase PCR on native nasal tissues. We conclude that Ca2-activated Cl−secretion in native human airway epithelia requires activation of Ca2-dependent basolateral Kchannels (hSK4). Co-activation of hKvLQT1 improves CaCC-mediated Cl−secretion in native CF airway epithelia, and may have a therapeutic effect in the treatment of CF lung disease.
Details
- Language :
- English
- ISSN :
- 00313998 and 15300447
- Volume :
- 53
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Pediatric Research (Ovid)
- Publication Type :
- Periodical
- Accession number :
- ejs49458925
- Full Text :
- https://doi.org/10.1203/01.PDR.0000057204.51420.DC