Fj. Mcdonald et al., CLONING, EXPRESSION, AND TISSUE DISTRIBUTION OF A HUMAN AMILORIDE-SENSITIVE NA+ CHANNEL, The American journal of physiology, 266(6), 1994, pp. 120000728-120000734
Amiloride-sensitive Na+ channels control, in part, fluid and electroly
te transport across epithelia in many organs. In the lung, they contro
l the quantity and composition of the respiratory tract fluid and play
a key role in the transition from a fluid-filled lung at the time of
birth. Their function may also be altered in a number of diseases. The
recent identification of an epithelial Na+ channel from rat colon all
owed us to use a probe from that sequence to clone an amiloride-sensit
ive Na+ channel from human kidney, alpha hENaC. The cDNA had an open r
eading frame of 2,007 nucleotides and encoded a protein predicted to c
ontain 669 amino acids. The amino acid sequence of alpha hENaC was 83%
identical to that of the rat. The gene was mapped to chromosome 12 by
polymerase chain reaction (PCR) of somatic cell hybrids. Transcripts
of alpha hENaC were detected in human kidney, lung, liver, and pancrea
s. No message was detected in first- and second-trimester human fetal
lung, indicating that alpha hENaC expression is developmentally regula
ted. In vitro transcription and translation of alpha hENaC produced a
74-kDa protein and translation in the presence of microsomal membranes
produced a glycosylated 87-kDa protein. Expression of alpha hENaC in
Xenopus oocytes produced currents that were amiloride sensitive and Na
+ selective, properties consistent with the function of epithelial Na channels in native tissues.