Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Physiol
2009 Jun 01;587Pt 11:2663-76. doi: 10.1113/jphysiol.2009.170324.
Show Gene links
Show Anatomy links
Regulation of epithelial sodium channels by cGMP/PKGII.
Nie HG
,
Chen L
,
Han DY
,
Li J
,
Song WF
,
Wei SP
,
Fang XH
,
Gu X
,
Matalon S
,
Ji HL
.
???displayArticle.abstract???
Airway and alveolar fluid clearance is mainly governed by vectorial salt movement via apically located rate-limiting Na(+) channels (ENaC) and basolateral Na(+)/K(+)-ATPases. ENaC is regulated by a spectrum of protein kinases, i.e. protein kinase A (PKA), C (PKC), and G (PKG). However, the molecular mechanisms for the regulation of ENaC by cGMP/PKG remain to be elucidated. In the present study, we studied the pharmacological responses of native epithelial Na(+) channels in human Clara cells and human alphabetagammadelta ENaCs expressed in oocytes to cGMP. 8-pCPT-cGMP increased amiloride-sensitive short-circuit current (I(sc)) across H441 monolayers and heterologously expressed alphabetagammadelta ENaC activity in a dose-dependent manner. Similarly, 8-pCPT-cGMP (a PKGII activator) but not 8-Br-cGMP (a PKGI activator) increased amiloride-sensitive whole cell currents in H441 cells in the presence of CFTRinh-172 and diltiazem. In all cases, the cGMP-activated Na(+) channel activity was inhibited by Rp-8-pCPT-cGMP, a specific PKGII inhibitor. This was substantiated by the evidence that PKGII was the sole isoform expressed in H441 cells at the protein level. Importantly, intratracheal instillation of 8-pCPT-cGMP in BALB/c mice increased amiloride-sensitive alveolar fluid clearance by approximately 30%, consistent with the in vitro results. We therefore conclude that PKGII is an activator of lung epithelial Na(+) channels, which may expedite the resolution of oedematous fluid in alveolar sacs.
Albert,
AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable channels in H441 human lung epithelial cell monolayers.
2008, Pubmed
Albert,
AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable channels in H441 human lung epithelial cell monolayers.
2008,
Pubmed
Barker,
Role of gammaENaC subunit in lung liquid clearance and electrolyte balance in newborn mice. Insights into perinatal adaptation and pseudohypoaldosteronism.
1998,
Pubmed
Canessa,
Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.
1994,
Pubmed
,
Xenbase
Cha,
cGMP inhibition of Na+/H+ antiporter 3 (NHE3) requires PDZ domain adapter NHERF2, a broad specificity protein kinase G-anchoring protein.
2005,
Pubmed
Chen,
Mechanisms of cystic fibrosis transmembrane conductance regulator activation by S-nitrosoglutathione.
2006,
Pubmed
Chen,
Influenza virus inhibits ENaC and lung fluid clearance.
2004,
Pubmed
Davis,
Respiratory syncytial virus induces insensitivity to beta-adrenergic agonists in mouse lung epithelium in vivo.
2007,
Pubmed
Fang,
Contribution of CFTR to apical-basolateral fluid transport in cultured human alveolar epithelial type II cells.
2006,
Pubmed
Firsov,
The heterotetrameric architecture of the epithelial sodium channel (ENaC).
1998,
Pubmed
,
Xenbase
French,
Isotype-specific activation of cystic fibrosis transmembrane conductance regulator-chloride channels by cGMP-dependent protein kinase II.
1995,
Pubmed
Gamm,
The type II isoform of cGMP-dependent protein kinase is dimeric and possesses regulatory and catalytic properties distinct from the type I isoforms.
1995,
Pubmed
Guo,
Nitric oxide inhibits Na+ absorption across cultured alveolar type II monolayers.
1998,
Pubmed
Hardiman,
Regulation of amiloride-sensitive Na(+) transport by basal nitric oxide.
2004,
Pubmed
Hardiman,
Lack of amiloride-sensitive transport across alveolar and respiratory epithelium of iNOS(-/-) mice in vivo.
2001,
Pubmed
Hummler,
Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice.
1996,
Pubmed
,
Xenbase
Itani,
Glucocorticoid-stimulated lung epithelial Na(+) transport is associated with regulated ENaC and sgk1 expression.
2002,
Pubmed
,
Xenbase
Jain,
Nitric oxide inhibits lung sodium transport through a cGMP-mediated inhibition of epithelial cation channels.
1998,
Pubmed
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Jernigan,
Pulmonary PKG-1 is upregulated following chronic hypoxia.
2003,
Pubmed
Ji,
The role of Pre-H2 domains of alpha- and delta-epithelial Na+ channels in ion permeation, conductance, and amiloride sensitivity.
2004,
Pubmed
,
Xenbase
Ji,
Delta-subunit confers novel biophysical features to alpha beta gamma-human epithelial sodium channel (ENaC) via a physical interaction.
2006,
Pubmed
Ji,
Point mutations in the post-M2 region of human alpha-ENaC regulate cation selectivity.
2001,
Pubmed
,
Xenbase
Junor,
Lack of a role for cyclic nucleotide gated cation channels in lung liquid absorption in fetal sheep.
2000,
Pubmed
Kamosinska,
Role of inducible nitric-oxide synthase in regulation of whole-cell current in lung epithelial cells.
2000,
Pubmed
Kemp,
Re-evaluating the Na(+) conductance of adult rat alveolar type II pneumocytes: evidence for the involvement of cGMP-activated cation channels.
2001,
Pubmed
Kosari,
Subunit stoichiometry of the epithelial sodium channel.
1998,
Pubmed
,
Xenbase
Kunzelmann,
Influenza virus inhibits amiloride-sensitive Na+ channels in respiratory epithelia.
2000,
Pubmed
Lazrak,
cAMP-induced changes of apical membrane potentials of confluent H441 monolayers.
2003,
Pubmed
Lazrak,
Biophysical properties and molecular characterization of amiloride-sensitive sodium channels in A549 cells.
2000,
Pubmed
Matthay,
Differential liquid and protein clearance from the alveoli of anesthetized sheep.
1982,
Pubmed
Matthay,
Invited review: Active fluid clearance from the distal air spaces of the lung.
2002,
Pubmed
McDonald,
Disruption of the beta subunit of the epithelial Na+ channel in mice: hyperkalemia and neonatal death associated with a pseudohypoaldosteronism phenotype.
1999,
Pubmed
Norlin,
Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats.
2001,
Pubmed
Rossier,
Epithelial sodium channel and the control of sodium balance: interaction between genetic and environmental factors.
2002,
Pubmed
Sakuma,
Malnutrition impairs alveolar fluid clearance in rat lungs.
2004,
Pubmed
Schlossmann,
cGMP-dependent protein kinases in drug discovery.
2005,
Pubmed
Schwiebert,
cGMP stimulates sodium and chloride currents in rat tracheal airway epithelia.
1997,
Pubmed
Sheng,
Extracellular Zn2+ activates epithelial Na+ channels by eliminating Na+ self-inhibition.
2004,
Pubmed
,
Xenbase
Snyder,
Electrophysiological and biochemical evidence that DEG/ENaC cation channels are composed of nine subunits.
1998,
Pubmed
,
Xenbase
Thomas,
cAMP-stimulated Na+ transport in H441 distal lung epithelial cells: role of PKA, phosphatidylinositol 3-kinase, and sgk1.
2004,
Pubmed
Thome,
Modulation of sodium transport in fetal alveolar epithelial cells by oxygen and corticosterone.
2003,
Pubmed
Tsubochi,
Early changes in alveolar fluid clearance by nitric oxide after endotoxin instillation in rats.
2003,
Pubmed
Vaandrager,
Membrane targeting of cGMP-dependent protein kinase is required for cystic fibrosis transmembrane conductance regulator Cl- channel activation.
1998,
Pubmed
Vaandrager,
cGMP stimulation of cystic fibrosis transmembrane conductance regulator Cl- channels co-expressed with cGMP-dependent protein kinase type II but not type Ibeta.
1997,
Pubmed
Woollhead,
Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells.
2007,
Pubmed
Xu,
Expression of cyclic nucleotide-gated cation channels in airway epithelial cells.
1999,
Pubmed
