A pore segment in DEG/ENaC Na+ channels

Abstract

DEG/ENaC Na+ channels have diverse functions, including Na+ absorption, neurotransmission, and sensory transduction. The ability of these channels to discriminate between different ions is critical for their normal function. Several findings suggest that DEG/ENaC channels have a pore structure similar to K+ channels. To test this hypothesis, we examined the accessibility of native and introduced cysteines in the putative P loop of ENaC. We identified residues that span a barrier that excludes amiloride as well as anionic and large methanethiosulfonate reagents from the pore. This segment contains a structural element ((S/G)CS) involved in selectivity of ENaC. The results are not consistent with predictions from the K+ channel pore, suggesting that DEG/ENaC Na+ channels have a novel pore structure.