Cp. Thomas et al., 5'-HETEROGENEITY IN EPITHELIAL SODIUM-CHANNEL ALPHA-SUBUNIT MESSENGER-RNA LEADS TO DISTINCT NH2-TERMINAL VARIANT PROTEINS, American journal of physiology. Cell physiology, 43(5), 1998, pp. 1312-1323
The amiloride-sensitive epithelial sodium channel (ENaC) is composed o
f three subunits: alpha, beta, and gamma. The human alpha-ENaC subunit
is expressed as at least two transcripts (N. Voilley, E. Lingueglia,
G. Champigny, M. G. Mattei, R. Waldmann, M. Lazdunski, and P. Barbry.
Proc. Natl. Acad. Sci. USA 91: 247-251, 1994). To determine the origin
of these transcripts, we characterized the 5' end of the alpha-ENaC g
ene. Four transcripts that differ at their first exon were identified.
Exon 1A splices to exon 2 to form the 5' end of alpha-ENaC1, whereas
exon 1B arises separately and continues into exon 2 to form alpha-ENaC
2. Other variant mRNAs, alpha-ENaC3 and alpha-ENaC4, are formed by act
ivating 5' splice sites within exon 1B. Although alpha-ENaC3 and -4 di
d not change the open reading frame for alpha-ENaC, alpha-ENaC2 contai
ns upstream ATGs that add 59 amino acids to the previous (alpha-ENaC1)
protein. To address the significance of these isoforms, both proteins
were expressed in Xenopus oocytes. The cRNA for each alpha-ENaC trans
cript when combined with beta- and gamma-ENac cRNA reconstituted a low
-conductance ion channel with amiloride-sensitive currents of similar
characteristics. We have thus identified variant alpha-ENaC mRNAs that
lead to functional ENaC peptides.