Regulation of Cl- secretion by AMPK in vivo

Patthara Kongsuphol, Bernhard Hieke, Jiraporn Ousingsawat, Joana Almaca, Benoit Viollet, Rainer Schreiber, Karl Kunzelmann

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Previous in vitro studies suggested that Cl- currents produced by the cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7) are inhibited by the α1 isoform of the adenosine monophosphate (AMP)-stimulated kinase (AMPK). AMPK is a serine/threonine kinase that is activated during metabolic stress. It has been proposed as a potential mediator for transport-metabolism coupling in epithelial tissues. All previous studies have been performed in vitro and thus little is known about the regulation of Cl- secretion by AMPK in vivo. Using AMPKα1-/- mice and wild-type littermates, we demonstrate that phenformin, an activator of AMPK, strongly inhibits cAMP-activated Cl- secretion in mouse airways and colon, when examined in ex vivo in Ussing chamber recordings. However, phenformin was equally effective in AMPKα1-/- and wild-type animals, suggesting additional AMPK-independent action of phenformin. Phenformin inhibited CFTR Cl- conductance in basolaterally permeabilized colonic epithelium from AMPKα1+/+ but not AMPKα1 -/- mice. The inhibitor of AMPK compound C enhanced CFTR-mediated Cl- secretion in epithelial tissues of AMPKα1-/- mice, but not in wild-type littermates. There was no effect on Ca 2+-mediated Cl- secretion, activated by adenosine triphosphate or carbachol. Moreover CFTR-dependent Cl- secretion was enhanced in the colon of AMPKα1-/- mice, as indicated in Ussing chamber ex vivo and rectal PD measurements in vivo. Taken together, these data suggest that epithelial Cl- secretion mediated by CFTR is controlled by AMPK in vivo.

Original languageEnglish (US)
Pages (from-to)1071-1078
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume457
Issue number5
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

Keywords

  • AMPK
  • CFTR
  • Cystic fibrosis transmembrane conductance regulator

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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    Kongsuphol, P., Hieke, B., Ousingsawat, J., Almaca, J., Viollet, B., Schreiber, R., & Kunzelmann, K. (2009). Regulation of Cl- secretion by AMPK in vivo. Pflugers Archiv European Journal of Physiology, 457(5), 1071-1078. https://doi.org/10.1007/s00424-008-0577-3