“ENaC Silencing as a Strategy to Correct the Airway Surface Fluid Defecit in Cystic Fibrosis:

– In the respiratory system, Na+ absorption and Cl- secretion are balanced in order to maintain an appropriate airway surface fluid (ASF) volume and ensure an efficient mucociliary clearance.
– In cystic fibrosis (CF), this equilibrium is disrupted by mutations in the CFTR gene resulting in the absence of functional CFTR-dependent Cl- secretion.
– The consequences of defective Cl- transport are worsened by the persistence of Na+ absorption which contributes to airway surface dehydration.”

This study looked at restoring the ASF through recovering chloride secretion or by reducing sodium absorption. The results showed that:
1) It was possible to reduce sodium channel (ENaC) transcripts- therefore less sodium channels leading to less sodium absorption
2) Decreasing the sodium absorption lead to an increase of the ASF (from nearly 7 µm to more than 9 µm)
3) The ASF thickness was about half of non-CF (10-14 µm)
4) Reducing sodium absorption increased the ASF to the same extent as recovering chloride secretion through CFTR rescue (correctors/potentiators)
These results “indicate that CFTR rescue and ENaC silencing both produce a significant and long-lasting increase of the airway hydration in vitro.”

Source: http://www.ncbi.nlm.nih.gov/pubmed/23600628


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2. Sodium ENaC Channel