TY - JOUR T1 - Structure and pharmacological modulation of inhibitory glycine receptors JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.116.105726 SP - mol.116.105726 AU - Carlos F Burgos AU - Gonzalo E Yevenes AU - Luis G Aguayo Y1 - 2016/01/01 UR - http://molpharm.aspetjournals.org/content/early/2016/07/08/mol.116.105726.abstract N2 - Glycine receptors (GlyRs) are inhibitory Cys-loop ion channels that contribute to the control of excitability along the central nervous system (CNS). GlyRs are found in the spinal cord, brain stem and more recently were reported in higher regions of the CNS such as hippocampus and nucleus accumbens. GlyR are involved in motor coordination, respiratory rhythms, pain transmission, sensory processing and are targets for relevant physiological and pharmacological modulators. In recent years, several reports have shed light on the residues and mechanisms associated with the activation, blockade, and regulation of pentameric Cys-loop ion channels at the atomic level by protein crystallography and cryo-electron microscopy. Initial studies conducted on the extracellular domain of acetylcholine receptors, ion channels from prokaryote homologues (ELIC, GLIC), and crystallized eukaryotic receptors made it possible to define the overall structure and topology of the Cys-loop receptors. For example, the determination of pentameric GlyRs structures bound to glycine and strychnine have contributed to visualize the structural changes implicated in the transition between the open and closed states of the Cys-loop receptors. In this review, we summarize how the new information obtained in functional, mutagenesis and structural studies have contributed to a better understanding of the function and regulation of GlyRs. ER -