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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2016; 62(5): 19-26


G. Maleeva1,2, S. Buldakova1, G. Skibo2, P. Bregestovski1

  1. Institute de Neurosciences des Systemes, INSERM UMR 1106, Aix-Marseille Université, France ;
  2. Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv


Previously, we have shown that ginkgolic acid has an ability to potentiate currents, mediated by α1 subunits of glycine receptor. In order to define the mechanism of subunit specific action of ginkgolic acid we have performed comparative analysis of the amino acid sequences of α1 and α2 subunits of glycine receptor. Amino acids that contribute to the different action of ginkgolic acid on glycine receptors formed by these subunits were determined. Using whole-cell configuration of patch-clamp recording, we have demonstrated that mutation of three residues in α2 subunit for corresponding ones from α1 subunit makes α2 receptors sensitive to the potentiation by ginkgolic acid. Сurrents, mediated by α2 mutant receptors, increased by 89±14% after application of ginkgolic acid. Similarly to α1 receptors α2 mutant receptors have shown a decrease in EC50 for glycine under the action of ginkgolic acid. Thus, subunit selectivity of the ginkgolic acid is in strong connection with three amino acid residues that are different in α1 and α2 subunits of glycine receptor.

Keywords: glycine receptor; ginkgolic acid; ionic currents; patch-clamp; point mutations.


  1. Malosio M, Marqueze-Pouey B, Kuhse J, Betz H.Wide spread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J. 1991; 10:2401–09.
  3. Betz H, Laube B. Glycine receptors: recent insights into their structural organization and functional diversity. J Neurochem. 2006; 97:1600–10. CrossRef PubMed
  5. Lynch JW. Molecular structure and function of the glycine receptor chloride channel. Physiol Rev. 2004; 84:1051–95. CrossRef PubMed
  7. Langosch D, Thomas L, Betz H. Conserved quaternary structure of ligand-gated ion channels: the postsynaptic glycine receptor is a pentamer. Proc Natl Acad Sci USA. 1988; 85:7394–98. CrossRef PubMed PubMedCentral
  9. Haeger S, Kuzmin D, Detro-Dassen S, Lang N, Kilb M, Tsetlin V, Betz H, Laube B, Schmalzing G. An intramembrane aromatic network determines pentameric assembly of Cys-loop receptors. Nat Struct Mol Biol. 2010; 17(1):90-8. CrossRef PubMed
  11. Grenningloh G, Pribilla I, Prior P, Multhaup G, Beyreuther K, Taleb O, Betz H. Cloning and expression of the 58 kd β subunit of the inhibitory glycine receptor. Neuron. 1990; 4(6):963-70. CrossRef  
  12. Grudzinska J, Schemm R, Haeger S, Nicke A, Schmalzing G, Betz H, Laube B. The beta subunit determines the ligand binding properties of synaptic glycine receptors. Neuron. 2005; 45:727–39. CrossRef PubMed
  14. Dutertre S, Becker C-M, Betz H. Inhibitory glycine receptors: an update. J Biol Chem. 2012; 287:40216–23. CrossRef PubMed PubMedCentral
  16. Schaefer N, Vogel N and Villmann C. Glycine receptor mutants of the mouse: what are possible routs of inhibitory compensation? Front Mol Neurosc. 2012; doi: 10.3389/ fnmol.2012.00098.
  18. Shiang R, Ryan S, Zhu Y-Z, Hahn A, O'Connell P, Wasmuth J. Mutations in the alpha subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nat Gen. 1993; 5:351-8. CrossRef PubMed
  20. Laube B, Maksay G, Schemm R, Betz H. Modulation of glycine receptor function: a novel approach for therapeutic intervention at inhibitory synapses? Trends Pharmacol Sci. 2002; 23:519–27.
  22. Maleeva G, Buldakova S, Bregestovski P. Selective potentiation of alpha 1 glycine receptors by ginkgolic acid. Front Mol Neurosc. 2015; doi: 10.3389/fnmol.2015.00064. CrossRef  
  23. Yevenes GE, Zeilhofer HU. Allosteric modulation of glycine receptors. Br J Pharmacol. 2011; 164:224-36. CrossRef PubMed PubMedCentral
  25. Rundstrom N, Schmieden V, Betz H, Bormann J, Langosch D. Cyanotriphenylborate: Sybtype-specific blocker of glycine receptor chloride channes. PNAS. 1994; 91:8950-4. CrossRef PubMed PubMedCentral
  27. Yang Z, Cromer B, Harvey R, Parker M, Lynch J. A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. J Neurochem. 2007; 103:580-9. CrossRef PubMed
  29. Xiong W, Cheng K, Cui T, Godlewski G, Rice KC, Xu Y, Zhang L. Cannabinoid potentiation of glycine receptors contributes to cannabis-induced analgesia. Nat Chem Biol. 2011; 7(5):296-303. CrossRef PubMed PubMedCentral
  31. Mascia MP, Mihic SJ, Valenzuela CF, Schofield PR, Harris RA. A single aminoacid determines differences in ethanol actions on strychnine-sensitive glycine receptors. Mol Pharmacol. 1996; 50(2):402-6.
  33. Yevenes GE, Zeilhofer HU. Molecular sites for the positive allosteric modulation of glycine receptors by endocannabinoids. PloSOne. 2011; 6: e23886.
  35. Webb TI, Lynch JW. Molecular pharmacology of the glycine receptor chloride channel. Curr Pharm Des. 2007; 13(23):2350-67. CrossRef  
  36. Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE, Mascia MP, Valenzuela CF, Hanson KK, Greenblatt EP, Harris RA, Harrison NL. Sites of alcohol and volatile anaesthetic actionon GABA(A) and glycine receptors. Nature. 1997; 389(6649):385-9. CrossRef PubMed
  38. Fuenteabla J, Munoz B, Yevenes G, Moraga-Cid G, Perez C, Guzman L, Rigo JM, Aguayo LG. Potentiation and inhibition of glycine receptors by tutin. Neuropharmacology. 2011; 60:453-9. CrossRef PubMed
  40. Du J, Lu W, Wu S, Cheng Y, Gouaux E. Glycine receptor mechanism elucidated by electron cryo-mycroscopy. Nature. 2015; doi:10.1038/nature14853. CrossRef  
  41. Bormann J, Rundstrom N, Betz H, Langosch D. Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo- and heterooligomers. EMBO J. 1993; 12:3729-37.

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