Glycine receptor

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The glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brainstem.[1]

The receptor can be activated by a range of simple amino acids including glycine, β-alanine and taurine, and can be selectively blocked by the high-affinity competitive antagonist strychnine.[2] Caffeine has recently been found to also be a competitive antagonist of GlyR.[3]

GlyR is known to colocalize with the GABAA receptor on some hippocampal neurons.[4] Gephyrin has been shown to be necessary for GlyR clustering at inhibitory synapses.[4][5]

Arrangement of subunits[edit]

Strychnine-sensitive GlyRs are members of a family of ligand-gated ion channels. Receptors of this family are arranged as five subunits surrounding a central pore, with each subunit composed of four α helical transmembrane segments.[6] There are presently four known isoforms of the α-subunit (α1-4) of GlyR that are essential to bind ligands (GLRA1, GLRA2, GLRA3, GLRA4) and a single β-subunit (GLRB).

The adult form of the GlyR is the heteromeric α1β receptor, which is believed to have a stoichiometry (proportion) of three α1 subunits and two β subunits [7] or four α1 subunits and one β subunit.[8] The α-subunits are also able to form functional homo-pentameric receptors in heterologous expression systems in African clawed frog's oocytes or mammalian cell lines,[8] and the α1 homomeric receptor is essential for studies of channel pharmacokinetics and pharmacodynamics.[9]

Glycine receptors in diseases[edit]

Disruption of GlyR surface expression or reduced ability of expressed GlyRs to conduct chloride ions results in the rare neurological disorder, hyperekplexia. The disorder is characterized by an exaggerated response to unexpected stimuli which is followed by a temporary but complete muscular rigidity often resulting in an unprotected fall. Chronic injuries as a result of the falls are symptomatic of the disorder.[1] A mutation in GLRA1 is responsible for some cases of stiff person syndrome.[10]

Ligands[edit]

Agonists[edit]

Antagonists[edit]

References[edit]

  1. ^ a b Lynch JW (October 2004). "Molecular structure and function of the glycine receptor chloride channel". Physiological reviews 84 (4): 1051–95. doi:10.1152/physrev.00042.2003. PMID 15383648. 
  2. ^ Rajendra, S; Lynch JW; Schofield PR (1997). "The glycine receptor". Pharmacology and Therapeutics 73 (2): 121–146. doi:10.1016/S0163-7258(96)00163-5. PMID 9131721. 
  3. ^ Duan L, Yang J, Slaughter MM. (2009). Caffeine inhibition of ionotropic glycine receptors. J Physiol. 587(Pt 16):4063-75. doi:10.1113/jphysiol.2009.174797 PMID 19564396
  4. ^ a b
    1. REDIRECT Template:Cite pmid
  5. ^ Feng G, Tintrup H, Kirsch J, et al. (November 1998). "Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity". Science 282 (5392): 1321–4. Bibcode:1998Sci...282.1321F. doi:10.1126/science.282.5392.1321. PMID 9812897. 
  6. ^ Miyazawa, A; Fujiyoshi Y; Unwin N (2003). "Structure and gating mechanism of the acetylcholine receptor pore". Nature 423 (6943): 949–955. Bibcode:2003Natur.423..949M. doi:10.1038/nature01748. PMID 12827192. 
  7. ^ Kuhse, J; Laube B; Magalei D; Betz H (1993). "Assembly of the inhibitory glycine receptor: identification of amino acid sequence motifs governing subunit stoichiometry". Neuron 11 (6): 1049–1056. doi:10.1016/0896-6273(93)90218-G. PMID 8274276. 
  8. ^ a b Kuhse, J; Betz H; Kirsch J (1995). "The inhibitory glycine receptor: architecture, synaptic localization and molecular pathology of a postsynaptic ion-channel complex". Current Opinion in Neurobiology 5 (3): 318–323. doi:10.1016/0959-4388(95)80044-1. PMID 7580154. 
  9. ^ Lewis, TM; Schofield PR; McClellan AM (2003). "Kinetic determinants of agonist action at the recombinant human glycine receptor". Journal of Physiology 549 (Part 2): 361–374. doi:10.1113/jphysiol.2002.037796. PMC 2342959. PMID 12679369. Retrieved 2007-01-16. 
  10. ^ Online 'Mendelian Inheritance in Man' (OMIM) STIFF-PERSON SYNDROME; SPS -184850

External links[edit]