cAMP-dependent activation of CFTR inhibits the epithelial sodium channel (ENaC) without affecting its surface expression

Autor: Angelos-Aristeidis Konstas, Jan-Peter Koch, Christoph Korbmacher
Rok vydání: 2003
Předmět:
inorganic chemicals
Epithelial sodium channel
congenital
hereditary
and neonatal diseases and abnormalities
medicine.medical_specialty
Patch-Clamp Techniques
Physiology
Clinical Biochemistry
Xenopus
Cystic Fibrosis Transmembrane Conductance Regulator
Gene Expression
Stimulation
medicine.disease_cause
Sodium Channels
Xenopus laevis
Physiology (medical)
Internal medicine
Hyperaldosteronism
Cyclic AMP
medicine
Animals
Humans
Epithelial Sodium Channels
Receptor
Mutation
biology
urogenital system
Chemistry
Membrane Proteins
respiratory system
biology.organism_classification
Molecular medicine
Cystic fibrosis transmembrane conductance regulator
Rats
Endocrinology
Luminescent Measurements
Oocytes
Potassium
biology.protein
Surface expression
Ion Channel Gating
hormones
hormone substitutes
and hormone antagonists
Zdroj: Pflügers Archiv - European Journal of Physiology. 445:513-521
ISSN: 1432-2013
0031-6768
DOI: 10.1007/s00424-002-0957-z
Popis: The cystic fibrosis transmembrane conductance regulator (CFTR) is thought to modulate epithelial sodium channel (ENaC) function in various preparations. However, the molecular nature and (patho-)physiological significance of the CFTR/ENaC interaction is still unclear and may vary in different tissues. Co-expression experiments in Xenopus laevis oocytes are a popular approach to investigate a possible functional interaction of CFTR and ENaC but have revealed controversial results. We could confirm previous reports that in oocytes co-expressing ENaC and CFTR the amiloride-sensitive current was reduced during cAMP-mediated stimulation of CFTR. In contrast, co-expression of CFTR per se had no effect on baseline ENaC currents. ENaC with Liddle's syndrome mutation is also inhibited during activation of CFTR, suggesting that the C-terminus of the ENaC beta-subunit is not important for this functional interrelation. Single-channel patch-clamp recordings demonstrated that co-expression of CFTR does not alter the single-channel conductance of ENaC. Using a chemiluminescence assay we demonstrated that the inhibition of ENaC during cAMP-dependent activation of CFTR was not associated with a decrease in ENaC surface expression. We conclude that the inhibitory effect of cAMP-activated CFTR on ENaC is due to a decrease in channel open probability.
Databáze: OpenAIRE
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