Aqueous cigarette smoke extract induces a voltage-dependent inhibition of CFTR expressed in Xenopus oocytes

A. R. Moran, Y. Norimatsu, D. C. Dawson, Kelvin Macdonald

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel inhabits the apical membrane of airway epithelia, where its function is essential for mucus hydration, mucociliary clearance, and airway defense. Chronic obstructive pulmonary disease (COPD), most often a consequence of cigarette smoke (CS) exposure, affects 15 million persons in the US. Clinically, COPD is characterized by many of the salient features of cystic fibrosis lung disease, where CFTR is either absent or reduced in function. CS is an acidic aerosol (pH 5.3 to 6.3) reported to contain over 4,000 constituents. Acute CS exposure has been reported to decrease airway transepithelial voltage in vivo and short-circuit current in vitro; however, the mechanistic basis of these effects is uncertain. The goal of the studies described here was to develop a bioassay to characterize the effects of aqueous CS preparations on the channel function of CFTR. We studied aqueous CS extract (CSE) prepared in our laboratory, as well as commercial cigarette smoke condensate (CSC) in Xenopus oocytes expressing human CFTR. Application of CSE at pH 5.3 produced a reversible, voltage-dependent inhibition of CFTR conductance. CSE neutralized to pH 7.3 produced less inhibition of CFTR conductance. Serial dilution of CSE revealed a dose-dependent effect at acidic and neutral pH. In contrast, CSC did not inhibit CFTR conductance in oocytes. We conclude that one or more components of CSE inhibits CFTR in a manner similar to diphenylamine-2-carboxylate, a negatively charged, open-channel blocker.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume306
Issue number3
DOIs
StatePublished - Feb 1 2014

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Xenopus
Smoke
Tobacco Products
Oocytes
Chronic Obstructive Pulmonary Disease
Mucociliary Clearance
Chloride Channels
Mucus
Aerosols
Cystic Fibrosis
Biological Assay
Lung Diseases
Epithelium
Membranes

Keywords

  • CFTR
  • CIC-2
  • Cigarette smoke
  • pH

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Aqueous cigarette smoke extract induces a voltage-dependent inhibition of CFTR expressed in Xenopus oocytes. / Moran, A. R.; Norimatsu, Y.; Dawson, D. C.; Macdonald, Kelvin.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 306, No. 3, 01.02.2014.

Research output: Contribution to journalArticle

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