Lateral fenestrations in the extracellular domain of the glycine receptor contribute to the main chloride permeation pathway.

ABSTRACT: Glycine receptors (GlyRs) are ligand-gated ion channels mediating signal transduction at chemical synapses. Since the early patch-clamp electrophysiology studies, the details of the ion permeation mechanism have remained elusive. Here, we combine molecular dynamics simulations of a zebrafish GlyR-α1 model devoid of the intracellular domain with mutagenesis and single-channel electrophysiology of the full-length human GlyR-α1. We show that lateral fenestrations between subunits in the extracellular domain provide the main translocation pathway for chloride ions to enter/exit a central water-filled vestibule at the entrance of the transmembrane channel. In addition, we provide evidence that these fenestrations are at the origin of current rectification in known anomalous mutants and design d

SUBMITTER: Cerdan AH 

PROVIDER: S-EPMC9565810 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature