ArticleThe Journal of physiology2008
AICAR activates AMPK and alters PIP2 association with the epithelial sodium channel ENaC to inhibit Na+ transport in H441 lung epithelial cells.
Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Effects of modulators of AMP-activated protein kinase on TASK-1/3 and intracellular Ca(2+) concentration in rat carotid body glomus cells.Respiratory physiology & neurobiology · 2014Article
- Regulation of ion channels and transporters by AMP-activated kinase (AMPK).Channels (Austin, Tex.) · 2014Review
- AMPK couples plasma renin to cellular metabolism by phosphorylation of ACC1.American journal of physiology. Renal physiology · 2013Article
- Downregulation of the renal outer medullary K(+) channel ROMK by the AMP-activated protein kinase.Pflugers Archiv : European journal of physiology · 2013Article
- Hypotonic shock modulates Na(+) current via a Cl(-) and Ca(2+)/calmodulin dependent mechanism in alveolar epithelial cells.PloS one · 2013Article
- Phosphatidylinositol phosphate-dependent regulation of Xenopus ENaC by MARCKS protein.American journal of physiology. Renal physiology · 2012Article
- AMP-activated protein kinase (AMPK)-dependent and -independent pathways regulate hypoxic inhibition of transepithelial Na+ transport across human airway epithelial cells.British journal of pharmacology · 2012Article
- The gasotransmitter hydrogen sulphide decreases Na⁺ transport across pulmonary epithelial cells.British journal of pharmacology · 2012Article
- Gasotransmitters: novel regulators of epithelial na(+) transport?Frontiers in physiology · 2012Article
- Cleavage of endogenous γENaC and elevated abundance of αENaC are associated with increased Na⁺ transport in response to apical fluid volume expansion in human H441 airway epithelial cells.Pflugers Archiv : European journal of physiology · 2011Article
- Amiloride-sensitive sodium channels and pulmonary edema.Pulmonary medicine · 2011Article
- Interaction and interrelation of P2X7 and P2X4 receptor complexes in mouse lung epithelial cells.Cellular and molecular life sciences : CMLS · 2010Article
- Role of the energy sensor AMP-activated protein kinase in renal physiology and disease.American journal of physiology. Renal physiology · 2010Review
- Lipopolysaccharide modifies amiloride-sensitive Na+ transport processes across human airway cells: role of mitogen-activated protein kinases ERK 1/2 and 5.Pflugers Archiv : European journal of physiology · 2010Article
- Phosphatidylinositol (4,5)bisphosphate inhibits K+-efflux channel activity in NT1 tobacco cultured cells.Plant physiology · 2009Article
- 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 · 2008Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Changes in amiloride-sensitive epithelial Na(+) channel (ENaC) activity (NP(o)) in the lung lead to pathologies associated with dysregulation of lung fluid balance. UTP activation of purinergic receptors and hydrolysis of PIP(2) via activation of phospholipase C (PLC) or AICAR activation of AMP-activated protein kinase (AMPK) inhibited amiloride-sensitive Na(+) transport across human H441 epithelial cell monolayers. Neither treatment altered alpha, beta or gamma ENaC subunit abundance (N) in the apical membrane indicating that the mechanism of inhibition was via a change in channel open state probability (P(o)). We found that UTP depleted PIP(2) abundance in the apical membrane whilst activation of AMPK prevented the binding of beta and gamma ENaC subunits to PIP(2.) The association of PIP(2) with the ENaC subunits is required to maintain channel activity via P(o). Thus, these data show for the first time that AICAR activation of AMPK inhibits Na(+) transport via a mechanism that perturbs the PIP(2)-ENaC channel interaction to alter P(o). In addition, we show that dissociation of PIP(2) from ENaC together with activation of AMPK further reduced Na(+) transport by a secondary effect that correlated with ENaC subunit internalization. Thus, when PIP(2)-ENaC subunit interactions were compromised, ENaC protein retrieval was initiated, indicating that AMPK can modulate ENaC P(o) and N.
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