Cl^- and H⁺ coupling properties and subcellular localizations of wildtype and disease-associated variants of the voltage-gated Cl^-/H⁺ exchanger ClC-5.

ABSTRACT: Dent disease 1 (DD1) is caused by mutations in the CLCN5 gene encoding a voltage-gated electrogenic nCl^-/H⁺ exchanger ClC-5. Using ion-selective microelectrodes and Xenopus oocytes, here we studied Cl^-/H⁺ coupling properties of WT ClC-5 and four DD1-associated variants (S244L, R345W, Q629*, and T657S), along with trafficking and localization of ClC-5. WT ClC-5 had a 2Cl^-/H⁺ exchange ratio at a V_h of +40 mV with a [Cl^-]_out of 104 mm, but the transport direction did not reverse with a [Cl^-]_out of 5 mm, indicating that ClC-5-mediated exchange of two Cl^- out for one H⁺ in is not permissible. We hypothesized that ClC-5 and H⁺-ATP

SUBMITTER: Chang MH 

PROVIDER: S-EPMC7008381 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature