Genetic variation of the alpha subunit of the epithelial Na + channel influences exhaled Na + in healthy humans

William T. Foxx-Lupo, Courtney M. Wheatley, Sarah E. Baker, Nicholas A. Cassuto, Nicholas A. Delamere, Eric M. Snyder

Research output: Contribution to journalArticle

8 Scopus citations

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 languageEnglish (US)
Pages (from-to)205-211
Number of pages7
JournalRespiratory Physiology and Neurobiology
Volume179
Issue number2-3
DOIs
StatePublished - Dec 15 2011

Keywords

  • ADRB2
  • Airway surface fluid
  • Beta-agonist
  • Breath condensate
  • SCNN1A

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

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