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

- α3K, α3L, and α3L(P185L) glycine receptors were expressed in HEK 293 cells.
- Glucose potentiated α3L and α3K GlyR-mediated currents, shifting EC50 4- to 5- fold.
- The high-activity mutant α3L(P185L) was not further potentiated by glucose.
- Glucose was active below 10 mM, i.e. at physiological concentrations.
- Glycine receptor potentiation may account for glucose-mediated analgesia.

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.