Structures of the volume-regulated anion channel LRRC8A/D in activating and inhibiting conditions.

LRRC8A/D heteromeric channels are activated by cell swelling and modulated by sybodies, with a specific structure of four A and two D subunits revealing key conformational states.

• Why it matters: Understanding the structure and regulation of volume-regulated anion channels is crucial because they control cell volume and permeability to ions, amino acids, and drugs, impacting cell survival and drug delivery.
• What they did: The study used patch-clamp electrophysiology and structural analysis to investigate LRRC8A/D channels, identifying their subunit composition and how sybodies influence their activity and conformation.
• The result: Findings show D subunits weaken A subunit interactions to enhance activation, and sybodies can either stabilize closed states or promote opening, informing potential therapeutic modulation of these channels.