Genetic Variation of the Alpha Subunit of the Epithelial Na+ Channels Influences Exhaled Na+ in Healthy Humans

• Published in: Respiratory physiology & neurobiology Vol. 179; no. 2-3; pp. 205 - 211
• Main Authors: Foxx-Lupo, William T., Wheatley, Courtney M., Baker, Sarah E., Cassuto, Nicholas A., Delamere, Nicholas A., Snyder, Eric M.
• Format: Journal Article
• Language: English
• Published: 26.08.2011
• ISSN: 1569-9048; 1878-1519
• DOI: 10.1016/j.resp.2011.08.008

Epithelial Na + Channels (ENaC) are located on alveolar cells and are important in β 2 -adrenergic receptor-mediated lung fluid clearance through the removal of Na + from the alveolar airspace. Previous work has demonstrated that genetic variation of the alpha subunit of ENaC at amino acid 663 is important in channel function: cells with the genotype resulting in alanine at amino acid 663 (A663) demonstrate attenuated function when compared to genotypes with at least one allele encoding threonine (T663, AT/TT). We sought to determine the influence of genetic variation at position 663 of ENaC on exhaled Na + in healthy humans. Exhaled Na + was measured in 18 AA and 13 AT/TT subjects (age=27±8 vs. 30±10yrs., ht.=174±12 vs. 171±10cm., wt=68±12 vs. 73±14kg., BMI=22±3 vs. 25±4kg/m 2 , mean±SD, for AA and AT/TT, respectively). Measurements were made at baseline and at 30, 60 and 90 minutes following the administration of a nebulized β 2 -agonist (albuterol sulfate, 2.5mg diluted in 3ml normal saline). The AA group had a higher baseline level of exhaled Na + and a greater response to β 2 -agonist stimulation (baseline= 3.1±1.8 vs. 2.3±1.5mmol/l; 30min-post= 2.1±0.7 vs. 2.2±0.8mmol/l; 60min-post= 2.0±0.5 vs. 2.3±1.0mmol/l; 90min-post= 1.8±0.8 vs. 2.6±1.5mmol/l, mean±SD, for AA and AT/TT, respectively, p<0.05). The results are consistent with the notion that genetic variation of ENaC influences β 2 -adrenergic receptor stimulated Na + clearance in the lungs, as there was a significant reduction in exhaled Na + over time in the AA group.