Purinergic signaling underlies CFTR control of human airway epithelial cell volume

Gavin M. Braunstein, Akos Zsembery, Torry A. Tucker, Erik M. Schwiebert

Research output: Contribution to journalArticle

31 Citations (Scopus)


Background: Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function in cystic fibrosis (CF) causes dysregulation of multiple ion channels, water channels, and acid-base transporters in epithelia. As such, we hypothesized that dysregulation of many critical ion channels and transporters may cause defects in human airway epithelial cell volume regulation. Methods: Cell volume, regulatory volume decrease, and its regulation was assessed in real-time via Coulter Counter Multisizer III-driven electronic cell sizing in non-CF, CF, and CFTR-complemented CF human airway epithelial cells. SPQ halide fluorescence assay of hypotonicity-induced chloride efflux provided indirect validation of the cell volume assays. Results: CFTR, via autocrine ATP signaling, governs human airway epithelial cell volume regulation. Non-CF cells and wild-type (WT)-CFTR-transfected CF cells had normal regulatory volume decrease (RVD) responses that were attenuated by blockade of autocrine and paracrine purinergic signaling. In contrast, parental IB3-1 CF cells or IB3-1 cells expressing CFTR mutants (ΔF508, G551D, and S1455X) failed to RVD. CF cell RVD was rescued by agonists to P2Y G protein-coupled receptors and, more robustly, by agonists to P2X purinergic receptor channels. Conclusions: Loss of CFTR and CFTR-driven autocrine ATP signaling may underlie defective cell volume regulation and dysregulated ion, water, and acid-base transport in CF airway epithelia.

Original languageEnglish
Pages (from-to)99-117
Number of pages19
JournalJournal of Cystic Fibrosis
Issue number2
Publication statusPublished - Jun 1 2004


  • Calcium entry channels
  • Cystic fibrosis
  • P2X receptors
  • P2Y receptors
  • Regulatory volume decrease

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

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