Premium
Glucose is a positive modulator for the activation of human recombinant glycine receptors
Author(s) -
Breitinger Ulrike,
Raafat Karim M.,
Breitinger HansGeorg
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13215
Subject(s) - glycine receptor , receptor , glycine , fructose , chemistry , inhibitory postsynaptic potential , medicine , endocrinology , taurine , ligand gated ion channel , biochemistry , biology , ion channel , amino acid
The inhibitory glycine receptor (GlyR), a cys–loop ion channel receptor, mediates rapid synaptic inhibition in spinal cord, brainstem and higher centres of the mammalian central nervous system. Here, modulation of GlyR function by glucose and fructose was examined in recombinant alpha1 and alpha1/beta GlyRs using patch‐clamp methods. Glucose was a positive modulator of the receptor, reducing the average EC 50 for glycine up to 4.5‐fold. Glucose reduced cell‐to‐cell variability of glycine‐mediated currents by stabilizing receptors with low EC 50 . Pre‐incubation with sugars for several hours also produced augmentation of current responses that persisted after sugar removal. Potentiation by sugars was most significant in the range between 5 and 20 mM, with EC 50 values ~ 10 mM, i.e. at physiological levels. Addition of glucose had no significant influence on responses mediated by the other GlyR agonists like taurine, β‐alanine or ivermectin, indicating that glucose specifically augmented glycine receptor‐mediated responses, and did not act through indirect metabolic effects. Receptor modulation by glucose may account for differences in constants reported in the literature and may be clinically relevant for disorders with elevated blood glucose levels.Glucose and related sugars are essential metabolites. We identified glucose and fructose as positive modulators of the human inhibitory glycine receptor, a neuronal ligand‐gated ion channel. Receptor‐mediated currents were enhanced at physiological concentrations (~ 10 mM of sugar). Direct modulation of a synaptic receptor by glucose is relevant in clinical cases of elevated blood glucose, and may be considered in experimental protocols.