Glycine Receptors

Abstract

Absract The inhibitory glycine receptor is a ligand‐gated chloride channel of the cys‐loop receptor family. As a chloride‐selective channel, it mediates rapid synaptic inhibition in mammalian spinal cord, brainstem, higher brain centres and nonneuronal tissues. In recent years, our understanding of glycine receptors has steadily grown, adding considerable depth to our knowledge of receptor function, structure, cellular trafficking and tissue distribution. Furthermore, new roles for glycinergic transmission in higher brain function have been uncovered. Glycine receptors should no longer be considered only as mediators of spinal reflexes, but were also found to play an important role in the modulation of higher brain function, including vision, hearing and pain signalling. The identification of novel agonists and modulators underlines the relevance of the inhibitory glycine receptor as a therapeutic target. This review extends a previous article of this series and highlights key developments in glycine receptor research over the past 2–3 years. Key Concepts: Glycine receptors are key mediators of rapid synaptic inhibition in mammalian spinal cord and higher brain centres. Glycine receptors are members of the cys‐loop family of ligand‐gated ion channel receptors. Glycinergic signalling is involved in motor control, pain signalling, vision, hearing and other brain functions. Mutations in glycine receptor genes underlie human hyperekplexia and related myoclonic diseases. New modulators of glycine receptor function are rare and of considerable medicinal interest.

PKA and PKC Modulators Affect Ion Channel Function and Internalization of Recombinant Alpha1 and Alpha1-Beta Glycine Receptors

“…Native GlyRs are composed of two different subunits GlyR α (48 kDa) and β (58 kDa). Four different α subunits, α1-α4 and one β subunit are known to date (Breitinger, 2014 ), encoded by their respective genes GLRA1–4 and GLRB (Matzenbach et al, 1994 ). In addition, α-subunits can form functional homomeric ion channels while β-subunits are thought to be responsible of synaptic anchoring without having ion-channel function of their own (Breitinger and Becker, 2002 ; Grudzinska et al, 2005 ).…”

Modulation of Recombinant Human α1 Glycine Receptors by Mono- and Disaccharides: A Kinetic Study

“…The inhibitory glycine receptor is one of the principal mediators of rapid synaptic inhibition in the mammalian spinal cord and brain stem (1). Glycine receptors are pentameric ion channels that belong to the cys-loop family of ligand-gated ion channel receptors.…”

“…To date, four ligandbinding alpha subunits, α1-4, and one structural β-subunit are known, of which α4 is not expressed in humans. Each GlyR subunit contains an N-terminal extracellular domain, four transmembrane (TM) domains, as well as a large intracellular TM3-TM4 loop which is responsible for intracellular modulation (1)(2)(3). Under physiological conditions, the GlyR channel is primarily selective for chloride, leading to postsynaptic hyperpolarization (1)(2)(3).…”

Hierarchical Bloom Filter Trees for Approximate Matching

“…As a means of addressing these drawbacks, Breitinger, Rathgeb, and Baier (2014) presented a further article where they offered a theoretical solution to the lookup problem, based on a tree of Bloom filters. However, an implementation (and thus a validation) has not been conducted to date.…”

“…One way to improve upon the all-against-all comparison is to use the file-against-set strategy outlined by Breitinger, Baier, and White (2014). An alternative strategy that has not yet been fully evaluated is to use a hierarchical Bloom filter tree (HBFT), as suggested by Breitinger, Rathgeb, and Baier (2014). This approach is intended to achieve speed benefits over a pairwise comparison while supporting the identification of specific matching files.…”