Differential modulation of polycystin-2 gain-of-function channels by cysteine-reactive compounds, amphiphilic substances, and S4-S5 linker mutations.

ABSTRACT: Polycystin-2 (PC2) mutations are responsible for ∼15% of cases of autosomal-dominant polycystic kidney disease (ADPKD). PC2 belongs to the transient receptor potential ion channel family and can function as a homotetrameric nonselective cation channel. Little is known about its gating mechanism, and no specific PC2 activators or inhibitors have been identified. In this study, we performed a comparative electrophysiological analysis of two well-established gain-of-function PC2 constructs, PC2 F604P and PC2 L677A N681A, expressed in Xenopus laevis oocytes. Interestingly, PC2 F604P, but not PC2 L677A N681A, could be inhibited by several membrane-permeable cysteine-reactive compounds. In contrast, positively charged cysteine-reactive compounds had no inhibitory effect. Thus, the inhibitory eff

SUBMITTER: Geiges L 

PROVIDER: S-EPMC12597267 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature