Alveolar epithelial CNGA1 channels mediate cGMP-stimulated, amiloride-insensitive, lung liquid absorption
| Autor: | Yasuo Yamazaki, Daniela Riccardi, Olivier Staub, William J. Wilkinson, Ian De Proost, Paul J. Kemp, Dafydd V. Walters, M Orogo-Wenn, Dirk Adriaensen, A Benjamin, Takashi Morita |
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| Rok vydání: | 2011 |
| Předmět: |
Epithelial sodium channel
Male medicine.medical_specialty Patch-Clamp Techniques Physiology Veterinary medicine Clinical Biochemistry Cyclic Nucleotide-Gated Cation Channels Stimulation Absorption Amiloride 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals Humans Protein Isoforms Patch clamp Rats Wistar Diuretics Cyclic GMP Lung 030304 developmental biology Elapid Venoms 0303 health sciences Reabsorption Chemistry HEK 293 cells Biological Transport Epithelial Cells respiratory system Aquaporin 5 Rats Pulmonary Alveoli medicine.anatomical_structure Endocrinology HEK293 Cells Biophysics Female Ion Channel Gating 030217 neurology & neurosurgery Cation transport medicine.drug |
| Zdroj: | Pflugers Archiv : European journal of physiology Pflügers Archiv |
| ISSN: | 1432-2013 0031-6768 |
| Popis: | Impairment of lung liquid absorption can lead to severe respiratory symptoms, such as those observed in pulmonary oedema. In the adult lung, liquid absorption is driven by cation transport through two pathways: a well-established amiloride-sensitive Na+ channel (ENaC) and, more controversially, an amiloride-insensitive channel that may belong to the cyclic nucleotide-gated (CNG) channel family. Here, we show robust CNGA1 (but not CNGA2 or CNGA3) channel expression principally in rat alveolar type I cells; CNGA3 was expressed in ciliated airway epithelial cells. Using a rat in situ lung liquid clearance assay, CNG channel activation with 1 mM 8Br-cGMP resulted in an approximate 1.8-fold stimulation of lung liquid absorption. There was no stimulation by 8Br-cGMP when applied in the presence of either 100 μM l-cis-diltiazem or 100 nM pseudechetoxin (PsTx), a specific inhibitor of CNGA1 channels. Channel specificity of PsTx and amiloride was confirmed by patch clamp experiments showing that CNGA1 channels in HEK 293 cells were not inhibited by 100 μM amiloride and that recombinant αβγ-ENaC were not inhibited by 100 nM PsTx. Importantly, 8Br-cGMP stimulated lung liquid absorption in situ, even in the presence of 50 μM amiloride. Furthermore, neither l-cis-diltiazem nor PsTx affected the β2-adrenoceptor agonist-stimulated lung liquid absorption, but, as expected, amiloride completely ablated it. Thus, transport through alveolar CNGA1 channels, located in type I cells, underlies the amiloride-insensitive component of lung liquid reabsorption. Furthermore, our in situ data highlight the potential of CNGA1 as a novel therapeutic target for the treatment of diseases characterised by lung liquid overload. |
| Databáze: | OpenAIRE |
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