Augmentation of glycine receptor alpha3 currents suggests a mechanism for glucose-mediated analgesia

Ulrike Breitinger; Hans-Georg Breitinger

doi:10.1016/j.neulet.2015.11.051

Augmentation of glycine receptor alpha3 currents suggests a mechanism for glucose-mediated analgesia

Neurosci Lett. 2016 Jan 26:612:110-115. doi: 10.1016/j.neulet.2015.11.051. Epub 2015 Dec 2.

Authors

Ulrike Breitinger¹, Hans-Georg Breitinger²

Affiliations

¹ Department of Biochemistry, The German University in Cairo, Main Entrance of Al Tagamoa Al Khames, New Cairo 11835, Egypt.
² Department of Biochemistry, The German University in Cairo, Main Entrance of Al Tagamoa Al Khames, New Cairo 11835, Egypt. Electronic address: [email protected].

PMID: 26656729
DOI: 10.1016/j.neulet.2015.11.051

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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analgesics / pharmacology*
Dose-Response Relationship, Drug
Glucose / pharmacology*
HEK293 Cells
Humans
Mutagenesis, Site-Directed
Patch-Clamp Techniques
Receptors, Glycine / genetics
Receptors, Glycine / physiology*

Substances

Analgesics
Receptors, Glycine
glycine receptor alpha3 subunit
Glucose