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Oligopeptide Competition Assay for Phosphorylation Site Determination
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Oligopeptide Competition Assay for Phosphorylation Site Determination

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Regulation of Cl(-) secretion by AMPK in vivo

Patthara Kongsuphol1, Bernhard Hieke, Jiraporn Ousingsawat

  • 1Department of Physiology, University of Regensburg, Germany.

Pflugers Archiv : European Journal of Physiology
|August 30, 2008
PubMed

Insights

Adenosine monophosphate-activated kinase (AMPK) controls cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride secretion in vivo. This study reveals AMPK

Area of Science:

  • Physiology
  • Molecular Biology
  • Epithelial Biology

Background:

  • In vitro studies indicated adenosine monophosphate-activated kinase (AMPK) inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride currents.
  • AMPK, a metabolic stress-activated kinase, is proposed to link transport and metabolism in epithelial tissues.
  • Little is known about in vivo regulation of chloride secretion by AMPK due to limited in vivo studies.

Purpose of the Study:

  • To investigate the in vivo role of AMPKalpha1 in regulating epithelial chloride secretion.
  • To determine if AMPK activation or inhibition affects CFTR-dependent chloride transport in vivo and ex vivo.

Main Methods:

  • Utilized AMPKalpha1 knockout (AMPKalpha1(-/-)) and wild-type (WT) mice.
  • Performed ex vivo Ussing chamber recordings on mouse airways and colon.
  • Administered phenformin (AMPK activator) and compound C (AMPK inhibitor).
  • Measured cAMP-activated and Ca(2+)-mediated chloride secretion.
  • Conducted in vivo rectal potential difference (PD) measurements.

Main Results:

  • Phenformin inhibited cAMP-activated chloride secretion ex vivo in both WT and AMPKalpha1(-/-) mice, suggesting AMPK-independent effects.
  • Phenformin inhibited CFTR chloride conductance in WT but not AMPKalpha1(-/-) colonic epithelium.
  • Compound C enhanced CFTR-mediated chloride secretion in AMPKalpha1(-/-) mice, but not WT.
  • CFTR-dependent chloride secretion was enhanced in the colon of AMPKalpha1(-/-) mice both ex vivo and in vivo.

Conclusions:

  • Epithelial chloride secretion mediated by CFTR is regulated by AMPK in vivo.
  • AMPKalpha1 plays a significant role in controlling CFTR-dependent chloride transport.
  • Findings highlight the in vivo importance of the AMPK-CFTR interaction in epithelial function.

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