Regulation of airway mucosal hydration
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Danahay, Henry, Gosling, Martin and Paisley, Derek (2010) Regulation of airway mucosal hydration. Expert Review of Clinical Pharmacology, 3 (3). pp. 361-369. ISSN 1751-2433
Abstract
Ion channels control the hydration status of the airway epithelium through apical anion secretion and cation absorption which is accompanied by osmotically obligated water. The key channels in this process are the cystic fibrosis transmembrane conductance regulator (CFTR), which is principally responsible for chloride secretion by airway epithelial cells and the epithelial sodium channel (ENaC) which is responsible for the absorption of sodium ions. In Cystic Fibrosis (CF), defective CFTR-mediated chloride secretion and an accompanying upregulation in ENaC mediated sodium absorption results in a reduction in airway surface liquid volume, leading to poorly hydrated mucus and impaired mucociliary clearance. Restoration of normal airway hydration by modulation of ion channel activity represents an important therapeutic strategy for CF. CFTR corrector and potentiator compounds are being developed with the aim of recovering normal chloride secretion. Calcium activated chloride channels (CaCCs) are expressed by the respiratory epithelia and are reported to be upregulated in CF offering a ‘surrogate’ pathway for chloride secretion. TMEM16A has recently been described as a CaCC in the airway epithelium and as such represents an alternative target for restoring chloride secretion in CF. An alternative therapeutic strategy for CF is to inhibit ENaC, thereby blocking excessive sodium absorption. This can be acheived by direct blockade of ENaC or inhibition of the channel activating proteases (CAPs) whose activity regulates ENaC function. This article will describe the regulation of airway mucosal hydration by ion channels and the efforts currently underway to restore normal mucosal hydration in disease patients by modulating the function of these channels.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing); 12 months for institutional or subject based servers |
| Keywords: | Ion channel, Cystic Fibrosis, airway epithelium, hydration |
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| Date Deposited: | 13 Oct 2015 13:16 |
| Last Modified: | 13 Oct 2015 13:16 |
| URI: | https://oak.novartis.com/id/eprint/2320 |