The lung amiloride-sensitive Na+ channel: biophysical properties, pharmacology, ontogenesis, and molecular cloning.
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+ > or = to 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.
Voilley
N
N
Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia Antipolis, Valbonne, France.
Lingueglia
E
E
Champigny
G
G
Mattéi
M G
MG
Waldmann
R
R
Lazdunski
M
M
Barbry
P
P
D000584:Amiloride / Q000494:pharmacology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D055592:Biophysical Phenomena; D001703:Biophysics; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D015870:Gene Expression; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015222:Sodium Channels / Q000737:chemistry / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D014018:Tissue Distribution
D012333:RNA, Messenger; D011994:Recombinant Proteins; D015222:Sodium Channels; D000584:Amiloride