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.
Cpt-cAMP activates human epithelial sodium channels via relieving self-inhibition.
Molina R
,
Han DY
,
Su XF
,
Zhao RZ
,
Zhao M
,
Sharp GM
,
Chang Y
,
Ji HL
.
???displayArticle.abstract???
External Na(+) self-inhibition is an intrinsic feature of epithelial sodium channels (ENaC). Cpt-cAMP regulates heterologous guinea pig but not rat αβγ ENaC in a ligand-gated manner. We hypothesized that cpt-cAMP may eliminate the self-inhibition of human ENaC thereby open channels. Regulation of self-inhibition by this compound in oocytes was analyzed using the two-electrode voltage clamp and Ussing chamber setups. External cpt-cAMP stimulated human but not rat and murine αβγ ENaC in a dose- and external Na(+) concentration-dependent fashion. Intriguingly, cpt-cAMP activated human δβγ more potently than αβγ channels, suggesting that structural diversity in ectoloop between human α, δ, and those ENaC of other species determines the stimulating effects of cpt-cAMP. Cpt-cAMP increased the ratio of stationary and maximal currents. Mutants having abolished self-inhibition (β(ΔV348) and γ(H233R)) almost completely eliminated cpt-cAMP mediated activation of ENaC. On the other hand, mutants both enhancing self-inhibition and elevating cpt-cAMP sensitivity increased the stimulating effects of the compound. This compound, however, could not activate already fully opened channels, e.g., degenerin mutation (αβ(S520C)γ) and the proteolytically cleaved ENaC by plasmin. Cpt-cAMP activated native ENaC to the same extent as that for heterologous ENaC in human lung epithelial cells. Our data demonstrate that cpt-cAMP, a broadly used PKA activator, stimulates human αβγ and δβγ ENaC channels by relieving self-inhibition.
Bangel-Ruland,
Characterization of the epithelial sodium channel delta-subunit in human nasal epithelium.
2010, Pubmed
Bangel-Ruland,
Characterization of the epithelial sodium channel delta-subunit in human nasal epithelium.
2010,
Pubmed
Berdiev,
Subunit stoichiometry of a core conduction element in a cloned epithelial amiloride-sensitive Na+ channel.
1998,
Pubmed
,
Xenbase
Bianchi,
Protons at the gate: DEG/ENaC ion channels help us feel and remember.
2002,
Pubmed
Bubien,
Expression and regulation of normal and polymorphic epithelial sodium channel by human lymphocytes.
2001,
Pubmed
Bubien,
Liddle's disease: abnormal regulation of amiloride-sensitive Na+ channels by beta-subunit mutation.
1996,
Pubmed
Bubien,
Alpha-adrenergic receptors regulate human lymphocyte amiloride-sensitive sodium channels.
1998,
Pubmed
,
Xenbase
Caldwell,
Serine protease activation of near-silent epithelial Na+ channels.
2004,
Pubmed
Caldwell,
Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport.
2005,
Pubmed
Chen,
Inhibition of Na+ transport in lung epithelial cells by respiratory syncytial virus infection.
2009,
Pubmed
Chrabi,
Stimulation of epithelial sodium channel activity by the sulfonylurea glibenclamide.
1999,
Pubmed
,
Xenbase
Chraïbi,
Effects of 8-cpt-cAMP on the epithelial sodium channel expressed in Xenopus oocytes.
2001,
Pubmed
,
Xenbase
Chraïbi,
Na self inhibition of human epithelial Na channel: temperature dependence and effect of extracellular proteases.
2002,
Pubmed
,
Xenbase
Collier,
Extracellular protons regulate human ENaC by modulating Na+ self-inhibition.
2009,
Pubmed
,
Xenbase
Collier,
Extracellular chloride regulates the epithelial sodium channel.
2009,
Pubmed
,
Xenbase
Cucu,
External Ni2 + and ENaC in A6 cells: Na+ current stimulation by competition at a binding site for amiloride and Na+.
2003,
Pubmed
,
Xenbase
Cucu,
Opposite effects of Ni2+ on Xenopus and rat ENaCs expressed in Xenopus oocytes.
2005,
Pubmed
,
Xenbase
Dijkink,
The epithelial sodium channel (ENaC) is intracellularly located as a tetramer.
2002,
Pubmed
,
Xenbase
Firsov,
The heterotetrameric architecture of the epithelial sodium channel (ENaC).
1998,
Pubmed
,
Xenbase
Frindt,
Feedback regulation of Na channels in rat CCT. III. Response to cAMP.
1995,
Pubmed
Garty,
Characteristics and regulatory mechanisms of the amiloride-blockable Na+ channel.
1988,
Pubmed
Garty,
Regulation of the epithelial Na+ channel by aldosterone: open questions and emerging answers.
2000,
Pubmed
Han,
K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport.
2010,
Pubmed
,
Xenbase
Horisberger,
Epithelial sodium channel: a ligand-gated channel?
2004,
Pubmed
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Ji,
Point mutations in the post-M2 region of human alpha-ENaC regulate cation selectivity.
2001,
Pubmed
,
Xenbase
Ji,
Degenerin sites mediate proton activation of deltabetagamma-epithelial sodium channel.
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
Kleyman,
ENaC at the cutting edge: regulation of epithelial sodium channels by proteases.
2009,
Pubmed
Kosari,
Subunit stoichiometry of the epithelial sodium channel.
1998,
Pubmed
,
Xenbase
Li,
Bumetanide stimulation of sodium permeability of the apical membrane of toad urinary bladder.
1988,
Pubmed
Lingueglia,
Expression cloning of an epithelial amiloride-sensitive Na+ channel. A new channel type with homologies to Caenorhabditis elegans degenerins.
1993,
Pubmed
,
Xenbase
Lingueglia,
FMRFamide-gated sodium channel and ASIC channels: a new class of ionotropic receptors for FMRFamide and related peptides.
2006,
Pubmed
Lu,
Small molecule activator of the human epithelial sodium channel.
2008,
Pubmed
,
Xenbase
Maarouf,
Novel determinants of epithelial sodium channel gating within extracellular thumb domains.
2009,
Pubmed
,
Xenbase
Matulef,
Cyclic nucleotide-gated ion channels.
2003,
Pubmed
McMahon,
The plasminogen activator system and cancer.
2008,
Pubmed
Nie,
8-pCPT-cGMP stimulates alphabetagamma-ENaC activity in oocytes as an external ligand requiring specific nucleotide moieties.
2010,
Pubmed
,
Xenbase
Nie,
Regulation of epithelial sodium channels by cGMP/PKGII.
2009,
Pubmed
,
Xenbase
Passero,
Plasmin activates epithelial Na+ channels by cleaving the gamma subunit.
2008,
Pubmed
,
Xenbase
Planès,
Regulation of the epithelial Na+ channel by peptidases.
2007,
Pubmed
,
Xenbase
Renauld,
Ile481 from the guinea pig alpha-subunit plays a major role in the activation of ENaC by cpt-cAMP.
2008,
Pubmed
,
Xenbase
Roch,
Halothane directly modifies Na+ and K+ channel activities in cultured human alveolar epithelial cells.
2006,
Pubmed
Rossier,
Epithelial sodium channel and the control of sodium balance: interaction between genetic and environmental factors.
2002,
Pubmed
Rossier,
Activation of the epithelial sodium channel (ENaC) by serine proteases.
2009,
Pubmed
Segal,
Rat ENaC expressed in Xenopus laevis oocytes is activated by cAMP and blocked by Ni(2+).
2002,
Pubmed
,
Xenbase
Sheng,
External nickel inhibits epithelial sodium channel by binding to histidine residues within the extracellular domains of alpha and gamma subunits and reducing channel open probability.
2002,
Pubmed
,
Xenbase
Sheng,
Extracellular Zn2+ activates epithelial Na+ channels by eliminating Na+ self-inhibition.
2004,
Pubmed
,
Xenbase
Sheng,
Functional role of extracellular loop cysteine residues of the epithelial Na+ channel in Na+ self-inhibition.
2007,
Pubmed
,
Xenbase
Shetty,
Post-transcriptional regulation of urokinase mRNA. Identification of a novel urokinase mRNA-binding protein in human lung epithelial cells in vitro.
2000,
Pubmed
Shlyonsky,
Electrophysiological characterization of rat type II pneumocytes in situ.
2008,
Pubmed
Snyder,
Electrophysiological and biochemical evidence that DEG/ENaC cation channels are composed of nine subunits.
1998,
Pubmed
,
Xenbase
Staruschenko,
Fluorescence resonance energy transfer analysis of subunit stoichiometry of the epithelial Na+ channel.
2004,
Pubmed
Su,
Interregulation of proton-gated Na(+) channel 3 and cystic fibrosis transmembrane conductance regulator.
2006,
Pubmed
Svenningsen,
Plasmin in nephrotic urine activates the epithelial sodium channel.
2009,
Pubmed
,
Xenbase
Svenningsen,
Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations.
2009,
Pubmed
Vetter,
Mechanisms of electrolyte transport across the endometrium. I. Regulation by PGF2 alpha and cAMP.
1996,
Pubmed
Xie,
Inhibition of ENaC by intracellular Cl- in an MDCK clone with high ENaC expression.
2004,
Pubmed
Yamamura,
Protons activate the delta-subunit of the epithelial Na+ channel in humans.
2004,
Pubmed
,
Xenbase
