Abstract
Epithelial Na + channels (ENaC) are located in 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 years vs. 30±10 years; ht.=174±12cm vs. 171±10cm; wt.=68±12kg vs. 73±14kg; BMI=22±3kg/m 2 vs. 25±4kg/m 2, mean±SD, for AA and AT/TT, respectively). Measurements were made at baseline and at 30, 60 and 90min 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±1.8mmol/l vs. 2.3±1.5mmol/l; 30min-post=2.1±0.7mmol/l vs. 2.2±0.8mmol/l; 60min-post=2.0±0.5mmol/l vs. 2.3±1.0mmol/l; 90min-post=1.8±0.8mmol/l 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.
Original language | English (US) |
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Pages (from-to) | 205-211 |
Number of pages | 7 |
Journal | Respiratory Physiology and Neurobiology |
Volume | 179 |
Issue number | 2-3 |
DOIs | |
State | Published - Dec 15 2011 |
Externally published | Yes |
Bibliographical note
Funding Information:Funding for this work was provided by HL108962-01 and the University of Arizona Clinical Scholars program . We are grateful for the subjects who graciously donated their time and effort to participate in this study.
Keywords
- ADRB2
- Airway surface fluid
- Beta-agonist
- Breath condensate
- SCNN1A