Bicarbonate transport of airway surface epithelia in luminally perfused mice bronchioles

Libin Liu, Akiko Yamamoto, Makoto Yamaguchi, Itsuka Taniguchi, Nao Nomura, Miyuki Nakakuki, Yuka Kozawa, Tomoya Fukuyasu, Mayuko Higuchi, Erina Niwa, Tsutomu Tamada, Hiroshi Ishiguro

研究成果: Article査読

3 被引用数 (Scopus)


HCO3 secretion in distal airways is critical for airway mucosal defense. HCO3/H+ transport across the apical membrane of airway surface epithelial cells was studied by measuring intracellular pH in luminally microperfused freshly dissected mice bronchioles. Functional studies demonstrated that CFTR, ENaC, Cl–HCO3 exchange, Na+-H+ exchange, and Na+–HCO3 cotransport are involved in apical HCO3/H+ transport. RT-PCR of isolated bronchioles detected fragments from Cftr, α, β, γ subunits of ENaC, Ae2, Ae3, NBCe1, NBCe2, NBCn1, NDCBE, NBCn2, Nhe1, Nhe2, Nhe4, Nhe5, Slc26a4, Slc26a6, and Slc26a9. We assume that continuous decline of intracellular pH following alkaline load demonstrates time course of HCO3 secretion into the lumen which is perfused with a HCO3-free solution. Forskolin-stimulated HCO3 secretion was substantially inhibited by luminal application of CFTRinh-172 (5 μM), H2DIDS (200 μM), and amiloride (1 μM). In bronchioles from a cystic fibrosis mouse model, basal and acetylcholine-stimulated HCO3 secretion was substantially impaired, but forskolin transiently accelerated HCO3 secretion of which the magnitude was comparable to wild-type bronchioles. In conclusion, we have characterized apical HCO3/H+ transport in native bronchioles. We have demonstrated that cAMP-mediated and Ca2+-mediated pathways are involved in HCO3 secretion and that apical HCO3 secretion is largely mediated by CFTR and H2DIDS-sensitive Cl–HCO3 exchanger, most likely Slc26a9. The impairment of HCO3 secretion in bronchioles from a cystic fibrosis mouse model may be related to the pathogenesis of early lung disease in cystic fibrosis.

ジャーナルJournal of Physiological Sciences
出版ステータスPublished - 2022 12月

ASJC Scopus subject areas

  • 生理学


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