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The Lung Amiloride-Sensitive Na+Channel: Biophysical Properties, Pharmacology, Ontogenesis, and Molecular Cloning
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The Lung Amiloride-Sensitive Na+Channel: Biophysical Properties, Pharmacology, Ontogenesis, and Molecular Cloning
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Journal Article
The Lung Amiloride-Sensitive Na+Channel: Biophysical Properties, Pharmacology, Ontogenesis, and Molecular Cloning
1994
Overview
Water balance in the lung is controlled via active Na+and Cl-transport. Electrophysiological measurements on lung epithelial cells demonstrated the presence of a Na+channel that is inhibited by amiloride (K0.5= 90 nM) and some of its derivatives such as phenamil (K0.5= 19 nM) and benzamil (K0.5= 14 nM) but not by ethylisopropylamiloride. An amiloride-sensitive Na+channel of 4 pS was recorded from outside-out patches excised from the apical membrane. This channel is highly selective for Na+(PNa
+/PK+≥ 10). Isolation of a human lung cDNA led to the primary structure of the lung Na+channel. The corresponding protein is 669 residues long and has two large hydrophobic domains. An amiloride-sensitive Na+-selective current apparently identical to the one observed in lung epithelial cells was recorded after expression of the cloned channel in oocytes. The level of the mRNA for the Na+channel was highly increased from fetal to newborn and adult stages. This observation indicates that the increased Na+reabsorption that occurs at birth as a necessary event to pass to an air-breathing environment is probably associated with control of transcription of this Na+channel. The human gene for the lung Na+channel was mapped on chromosome 12p13.
Publisher
National Academy of Sciences of the United States of America,National Acad Sciences,National Academy of Sciences
Subject
/ Biological and medical sciences
/ Cell membranes. Ionic channels. Membrane pores
/ Cell structures and functions
/ Cloning
/ Fundamental and applied biological sciences. Psychology
/ Hum
/ Humans
/ Ion Channel Gating - drug effects
/ Lungs
/ Molecular and cellular biology
/ Oocytes
/ Sequence Homology, Amino Acid
/ Sequence Homology, Nucleic Acid
/ Sodium
/ Sodium Channels - drug effects
/ Sodium Channels - physiology
/ Water
