Two serial filters control P2X7 cation selectivity, Ser342 in the central pore and lateral acidic residues at the cytoplasmic interface.

ABSTRACT: The human P2X7 receptor (hP2X7R) is a homotrimeric cell surface receptor gated by extracellular ATP^4- with two transmembrane helices per subunit, TM1 and TM2. A ring of three S342 residues, one from each pore-forming TM2 helix, located halfway across the membrane bilayer, functions to close and open the gate in the apo and ATP^4--bound open states, respectively. The hP2X7R is selective for small inorganic cations, but can also conduct larger organic cations such as Tris⁺. Here, we show by voltage-clamp electrophysiology in Xenopus laevis oocytes that mutation of S342 residues to positively charged lysines decreases the selectivity for Na⁺ over Tris⁺, but maintains cation selectivity. Deep in the membrane, laterally below the S342

SUBMITTER: Markwardt F 

PROVIDER: S-EPMC11388005 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature