Description:
<jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>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 <jats:styled-content style="fixed-case">EC</jats:styled-content><jats:sub>50</jats:sub> for glycine up to 4.5‐fold. Glucose reduced cell‐to‐cell variability of glycine‐mediated currents by stabilizing receptors with low <jats:styled-content style="fixed-case">EC</jats:styled-content><jats:sub>50</jats:sub>. 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 <jats:styled-content style="fixed-case">EC</jats:styled-content><jats:sub>50</jats:sub> 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.</jats:p></jats:sec><jats:sec><jats:label /><jats:p><jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc13215-fig-0006-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>
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.</jats:p></jats:sec>