title: Augmentation of glycine receptor alpha3 currents suggests a mechanism for glucose-mediated analgesia.
abstract: The inhibitory glycine receptor (GlyR) mediates rapid synaptic inhibition in the mammalian central nervous system. Recently, glucose was identified as a positive modulator of α1 GlyRs. Here, recombinant human α3GlyRs with and without glucose treatment were studied using patch clamp methods. Similar to α1GlyRs, receptor variants α3L and α3K were potentiated by sugar. Glucose treatment reduced EC50 values of GlyR α3L and α3K by a factor of 4.5 and 3.3, respectively, without affecting maximum currents or desensitization. The high-activity mutant α3L(P185L) was not further potentiated by glucose. Potentiation of glycinergic signalling may underlie some of the analgetic effects of glucose.
authors.affiliation: Department of Biochemistry, The German University in Cairo, Main Entrance of Al Tagamoa Al Khames, New Cairo 11835, Egypt.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Breitinger
authors.affiliation: Department of Biochemistry, The German University in Cairo, Main Entrance of Al Tagamoa Al Khames, New Cairo 11835, Egypt. Electronic address: hans.breitinger@guc.edu.eg.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Breitinger
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D018009:Receptors, Glycine / Q000235:genetics / Q000502:physiology*
chemical_list: D000700:Analgesics; D018009:Receptors, Glycine; C113965:glycine receptor alpha3 subunit; D005947:Glucose
keywords: 3 subunit; 3(P185L); Allosteric modulation; Gain-of-function mutant α; Glucose as channel modulator; Glycine receptors α; Ligand-gated ion channels; Pain pathways