Disease-associated missense mutations in the pore loop of polycystin-2 alter its ion channel function in a heterologous expression system.

Polycystin-2 (PC2) is mutated in ∼15% of patients with autosomal dominant polycystic kidney disease (ADPKD). PC2 belongs to the family of transient receptor potential (TRP) channels and can function as a homotetramer. We investigated whether three disease-associated mutations (F629S, C632R, or R638C) localized in the channel's pore loop alter ion channel properties of human PC2 expressed in Xenopus laevis oocytes.

The small molecule activator S3969 stimulates the epithelial sodium channel by interacting with a specific binding pocket in the channel's β-subunit.

The epithelial sodium channel (ENaC) is essential for mediating sodium absorption in several epithelia. Its impaired function leads to severe disorders, including pseudohypoaldosteronism type 1 and respiratory distress. Therefore, pharmacological ENaC activators have potential therapeutic implications.

Regulation of distal tubule sodium transport: mechanisms and roles in homeostasis and pathophysiology.

Regulated Na transport in the distal nephron is of fundamental importance to fluid and electrolyte homeostasis. Further upstream, Na is the principal driver of secondary active transport of numerous organic and inorganic solutes. In the distal nephron, Na continues to play a central role in controlling the body levels and concentrations of a more select group of ions, including K, Ca, Mg, Cl, and HCO, as well as water.