The intracellular domain of homomeric glycine receptors modulates agonist efficacy.

ABSTRACT: Like other pentameric ligand-gated channels, glycine receptors (GlyRs) contain long intracellular domains (ICDs) between transmembrane helices 3 and 4. Structurally characterized GlyRs are generally engineered to have a very short ICD. We show here that for one such construct, zebrafish GlyR_EM, the agonists glycine, β-alanine, taurine, and GABA have high efficacy and produce maximum single-channel open probabilities greater than 0.9. In contrast, for full-length human α1 GlyR, taurine and GABA were clearly partial agonists, with maximum open probabilities of 0.46 and 0.09, respectively. We found that the elevated open probabilities in GlyR_EM are not due to the limited sequence differences between the human and zebrafish orthologs, but rather to replacement of the nati

SUBMITTER: Ivica J 

PROVIDER: S-EPMC7995613 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature