VX-445 (elexacaftor) inhibits chloride secretion across human bronchial epithelial cells by directly blocking KCa3.1 channels.

ABSTRACT: Cystic fibrosis (CF) is a genetic disorder resulting from mutations to the CF transmembrane regulator (CFTR) anion channel. CFTR correctors partially restore the folding and trafficking of mutant CFTR. We recently demonstrated that the correctors VX-445 and VX-121 directly potentiate large-conductance Ca²⁺-activated (BK_Ca) channels. We postulated that this could enhance the therapeutic potential of these drugs in the lung by increasing the driving force for transepithelial Cl^- secretion. Herein, we evaluated the effect of acute addition of VX-445 on forskolin- and 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one-mediated Cl^- secretion across primary human bronchial epithelial cells (HBEs) from wild type (WT) and F508del donors. Surprisingly

SUBMITTER: Kolski-Andreaco A 

PROVIDER: S-EPMC12275099 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature