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AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable channels in H441 human lung epithelial cell monolayers

Albert, AP; Woollhead, AM; Mace, OJ; Baines, DL (2008) AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable channels in H441 human lung epithelial cell monolayers. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 295 (5). L837 - L848. ISSN 1040-0605 https://doi.org/10.1152/ajplung.90353.2008
SGUL Authors: Albert, Anthony Paul Baines, Deborah

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Abstract

Transepithelial transport of Na+ across the lung epithelium via amiloride-sensitive Na+ channels (ENaC) regulates fluid volume in the lung lumen. Activators of AMP-activated protein kinase (AMPK), the adenosine monophosphate mimetic AICAR, and the biguanide metformin decreased amiloride-sensitive apical Na+ conductance (GNa+) in human H441 airway epithelial cell monolayers. Cell-attached patch-clamp recordings identified two distinct constitutively active cation channels in the apical membrane that were likely to contribute to GNa+: a 5-pS highly Na+ selective ENaC-like channel (HSC) and an 18-pS nonselective cation channel (NSC). Substituting NaCl with NMDG-Cl in the patch pipette solution shifted the reversal potentials of HSC and NSC, respectively, from +23 mV to −38 mV and 0 mV to −35 mV. Amiloride at 1 μM inhibited HSC activity and 56% of short-circuit current (Isc), whereas 10 μM amiloride partially reduced NSC activity and inhibited a further 30% of Isc. Neither conductance was associated with CNG channels as there was no effect of 10 μM pimoside on Isc, HSC, or NSC activity, and 8-bromo-cGMP (0.3–0.1 mM) did not induce or increase HSC or NSC activity. Pretreatment of H441 monolayers with 2 mM AICAR inhibited HSC/NSC activity by 90%, and this effect was reversed by the AMPK inhibitor Compound C. All three ENaC proteins were identified in the apical membrane of H441 monolayers, but no change in their abundance was detected after treatment with AICAR. In conclusion, activation of AMPK with AICAR in H441 cell monolayers is associated with inhibition of two distinct amiloride-sensitive Na+-permeable channels by a mechanism that likely reduces channel open probability.

Item Type: Article
Keywords: AMP-Activated Protein Kinases, Amiloride, Aminoimidazole Carboxamide, Biophysical Phenomena, Cell Line, Cell Membrane, Cyclic Nucleotide-Gated Cation Channels, Epithelial Cells, Epithelial Sodium Channels, Humans, Ion Channel Gating, Lung, Metformin, Patch-Clamp Techniques, Permeability, Ribonucleotides, Science & Technology, Life Sciences & Biomedicine, Physiology, Respiratory System, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, AMP-activated protein kinase, ENaC, ACTIVATED PROTEIN-KINASE, GATED CATION CHANNELS, SODIUM-CHANNEL, FLUID TRANSPORT, ION-TRANSPORT, ALPHA-SUBUNIT, A6 CELLS, II CELLS, ENAC, EXPRESSION
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
ISSN: 1040-0605
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Dates:
DateEvent
1 November 2008Published
Web of Science ID: WOS:000260535000013
Download EPMC Full text (HTML)
URI: https://openaccess.sgul.ac.uk/id/eprint/1813
Publisher's version: https://doi.org/10.1152/ajplung.90353.2008

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