Mechanisms underlying modulation of human GlyRα3 by Zn²⁺ and pH.

ABSTRACT: Glycine receptors (GlyRs) regulate motor control and pain processing in the central nervous system through inhibitory synaptic signaling. The subtype GlyRα3 expressed in nociceptive sensory neurons of the spinal dorsal horn is a key regulator of physiological pain perception. Disruption of spinal glycinergic inhibition is associated with chronic inflammatory pain states, making GlyRα3 an attractive target for pain treatment. GlyRα3 activity is modulated by numerous endogenous and exogenous ligands that consequently affect pain sensitization. To understand the mechanism of two such endogenous modulators, Zn²⁺ and protons, we have used cryo-electron microscopy to determine structures of full-length human GlyRα3 in various functional states. Whereas acidic pH reduces peak glycine r

SUBMITTER: Kindig K 

PROVIDER: S-EPMC11654702 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature