CFTR involvement in nasal potential differences in mice and pigs studied using a thiazolidinone CFTR inhibitor

Danieli B. Salinas, Nicoletta Pedemonte, Chatchai Muanprasat, Walter F. Finkbeiner, Dennis W. Nielson, A. S. Verkman

Research output: Contribution to journalArticlepeer-review

Abstract

Nasal potential difference (PD) measurements have been used to demonstrate defective CFTR function in cystic fibrosis (CF) and to evaluate potential CF therapies. We used the selective thiazolidinone CFTR inhibitor CFTR inh-172 to define the involvement of CFTR in nasal PD changes in mice and pigs. In normal mice infused intranasally with a physiological saline solution containing amiloride, nasal PD was -4.7 ± 0.7 mV, hyperpolarizing by 15 ± 1 mV after a low-Cl- solution, and a further 3.9 ± 0.5 mV after forskolin. CFTRinh-172 produced 1.1 ± 0.9- and 4.3 ± 0.7-mV depolarizations when added after low Cl- and forskolin, respectively. Systemically administered CFTR inh-172 reduced the forskolin-induced hyperpolarization from 4.7 ± 0.4 to 0.9 ± 0.1 mV but did not reduce the low Cl --induced hyperpolarization. Nasal PD was -12 ± 1 mV in CF mice after amiloride, changing by - or forskolin. In pigs, nasal PD was -14 ± 3 mV after amiloride, hyperpolarizing by 13 ± 2 mV after low Cl- and a further 9 ± 1 mV after forskolin. CFTRinh-172 and glibenclamide did not affect nasal PD in pigs. Our results suggest that cAMP-dependent nasal PDs in mice primarily involve CFTR-mediated Cl- conductance, whereas cAMP-independent PDs are produced by a different, but CFTR-dependent, Cl - channel. In pigs, CFTR may not be responsible for Cl- channel-dependent nasal PDs. These results have important implications for interpreting nasal PDs in terms of CFTR function in animal models of CFTR activation and inhibition.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume287
Issue number5 31-5
DOIs
Publication statusPublished - Nov 2004

Keywords

  • Chloride channels
  • Cystic fibrosis
  • Cystic fibrosis transmembrane conductance regulator
  • Nasal potential difference

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Fingerprint

Dive into the research topics of 'CFTR involvement in nasal potential differences in mice and pigs studied using a thiazolidinone CFTR inhibitor'. Together they form a unique fingerprint.

Cite this