Fine-Tuning of Neuronal Ion Channels-Mapping of Residues Involved in Glucose Sensitivity of Recombinant Human Glycine Receptors.

The inhibitory glycine receptor (GlyR) mediates synaptic inhibition in the spinal cord, brain stem, and other regions of the mammalian central nervous system. Glucose was shown to potentiate α1 GlyRs by interacting with K143. Here, additional amino acids involved in glucose modulation were identified using a structure-based approach of site-directed mutagenesis followed by whole-cell patch-clamp analysis. We identified two additional lysine residues in the α1 GlyR extracellular domain, K16 and K281, that were involved in glucose modulation. Mutation of either residue to alanine abolished glucose potentiation. Residue K281 is located in the same pocket as K143 and could thus contribute to glucose binding. The double mutant K143A-K281A showed a 6-fold increase of EC