Function, Modulation, and Pharmacology of Inhibitory Glycine Receptor Channels

Ion channels of the glycine receptors (GlyR) provide an inhibitory drive in the nervous system of vertebrates. Four agonist-binding α subunits and one β subunit were cloned from the CNS of mammals (human, rat, and mouse), a bird (chicken), and a fish (zebrafish). The subunit composition determines the pharmacological properties of the GlyR and the function of the glycinergic synapses during development. Dysfunction of these receptors results in motor disorders (hyperekplexia, spasticity, and/or oscillatory phenomena), and mutations in the gene encoding the α subunit of GlyR underlie the molecular basis of these heritable diseases. Extra- and intracellular pharmacological tools can modulate the activity of GlyR channels. A recently discovered phenomenon of Ca-induced modulation of the GlyR suggests an important way of modulation of the activity of glycinergic synapses.