CLONING AND EXPRESSION OF THE BETA-SUBUNIT AND GAMMA-SUBUNIT OF THE HUMAN EPITHELIAL SODIUM-CHANNEL

Amiloride-sensitive Na+ channels are an important component of the Na reabsorption pathway in a number of epithelia. Here we report the clo ning and characterization of cDNAs encoding two subunits of the human kidney epithelial Na+ channel (beta- and gamma-hENaC). Their predicted amino acid sequences were highly homologous (83-85% identical) to the corresponding subunits reported from rat colon (beta- and gamma-rENaC ). Both beta- and gamma-hENaC mapped to human chromosome 16, Northern blot analysis showed high expression of beta- and gamma-hENaC in kidne y and lung and differential expression of the three subunits in other tissues. Coexpression of beta- and gamma-hENaC with alpha-hENaC in Xen opus oocytes produced Na+ channels with high selectivity for Na+ and h igh sensitivity to amiloride. In addition, human subunits were able to substitute for the corresponding rat subunits in forming functional N af channels, suggesting conservation of function and suggesting that d ifferences in sequence do not disrupt interactions between subunits. T hese results suggest that human alpha-, beta-, and gamma-hENaC togethe r form Na+ channels with properties that are similar to those observed in epithelia, and will allow further investigation into the role that these channels may play in human disease.