Extracellular Na + removal attenuates rundown of the epithelial Na + -channel (ENaC) by reducing the rate of channel retrieval
| Autor: | Angelos-Aristeidis Konstas, Tilmann Volk, Peter Bassalaý, Christoph Korbmacher, Heimo Ehmke |
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| Rok vydání: | 2004 |
| Předmět: |
inorganic chemicals
Epithelial sodium channel medicine.medical_specialty Physiology Clinical Biochemistry Endocytic cycle Xenopus Sodium Channels Xenopus laevis chemistry.chemical_compound Physiology (medical) Internal medicine medicine Extracellular Animals Liddle's syndrome Epithelial Sodium Channels Receptor biology urogenital system Sodium Extracellular Fluid respiratory system Brefeldin A Sodium Channel Agonists medicine.disease biology.organism_classification Cell biology Endocrinology chemistry Oocytes Female hormones hormone substitutes and hormone antagonists Intracellular |
| Zdroj: | Pfl�gers Archiv European Journal of Physiology. 447:884-894 |
| ISSN: | 1432-2013 0031-6768 |
| DOI: | 10.1007/s00424-003-1193-x |
| Popis: | Regulation of the epithelial sodium channel (ENaC) is important for the long-term control of arterial blood pressure as evidenced by gain of function mutations of ENaC causing Liddle's syndrome, a rare form of hereditary arterial hypertension. In Xenopus laevis oocytes expressing ENaC a spontaneous decline of ENaC currents over time, so-called rundown, is commonly observed. Mechanisms involved in rundown may be physiologically relevant and may be related to feedback regulation of ENaC by intra- or extracellular Na+. We tested the effect of extracellular Na+ removal on ENaC rundown. Spontaneous rundown of ENaC was largely prevented by extracellular Na+ removal and was partially prevented by primaquine suggesting that it is due to endocytic channel retrieval. Liddle's syndrome mutation caused a reduced rate of rundown, and in oocytes expressing the mutated channel extracellular Na+ removal not only prevented rundown but even increased the ENaC currents (runup). Acute exposure to high extracellular Na+ drastically reduced whole-cell currents and surface expression of wild-type ENaC, while these effects were much smaller in ENaC with Liddle's syndrome mutation consistent with a stabilization of the mutated channel in the plasma membrane. Interestingly, the apparent intracellular Na+ concentration [Na+](i-app) was high (60 mM) in ENaC-expressing oocytes but rundown was not associated with a further increase in [Na+](i-app). We conclude that the inhibitory effect of extracellular Na+ removal on rundown is due to an inhibition of endocytic ENaC retrieval. |
| Databáze: | OpenAIRE |
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