Abstract: | The -subunit of the amiloride-sensitive epithelialNa+ channel ( ENaC) is criticalin forming an ion conductive pore in the membrane. We have identifiedthe wild-type and three splice variants of the human ENaC (h ENaC)from the human lung cell line H441, using RT-PCR. These splice variantscontain various structures in the extracellular domain, resultingin premature truncation (h ENaCx), 19-amino acid deletion(h ENaC 19), and 22-amino acid insertion (h ENaC+22).Wild-type h ENaC and splice variants were functionally characterizedin Xenopus oocytes by coexpression with hENaC - and -subunits. Unlike wild-type h ENaC,undetectable or substantially reduced amiloride-sensitive currents wereobserved in oocytes expressing these splice variants. Wild-typeh ENaC was the most abundantly expressed h ENaC mRNA species in alltissues in which its expression was detected. These findings indicate that the extracellular domain is important to generate structural andfunctional diversity of h ENaC and that alternative splicing may playa role in regulating hENaC activity. |