EPITHELIAL SODIUM-CHANNEL REGULATORY PROTEINS IDENTIFIED BY FUNCTIONAL EXPRESSION CLONING

We describe here our current strategy for identifying and cloning prot eins involved in the regulation of the epithelial sodium channel (ENaC ). We have set up a complementation functional assay in the Xenopus la evis oocyte expression system. Using this assay, we have been able to identify a channel-activating protease (CAP-1) that can increase ENaC activity threefold. We propose a novel extracellular signal transducti on pathway controlling ionic channels of the ENaC gene family that inc lude genes involved in mechanotransduction (degenerins), in peptide-ga ted channels involved in neurotransmission (FaNaCh), in proton-gated c hannels involved in pH sensing (ASIC) or pain sensation (DRASIC).