Single-cell genetic expression of mutant GABAA receptors causing human genetic epilepsy alters dendritic spine and GABAergic bouton formation in a mutation-specific manner

Frontiers in Cellular Neuroscience

Volumn 8, Issue OCT, 2014, Pages

  Lachance Touchette, Pamela ^a   Choudhury, Mayukh ^b   Stoica, Ana ^a   Cristo, Graziella Di ^b   Cossette, Patrick ^a  

^a CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

^b UNIVERSITY OF MONTREAL   (Canada)

Author keywords

Bouton formation; Channelopathy; Epilepsy; GABAA receptor; Human genetics; Organotypic slice culture

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR;

4 AMINOBUTYRIC ACID A RECEPTOR ALPHA1 GENE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DENDRITIC SPINE; ELECTRON MICROSCOPY; EPILEPSY; GENE; GENE EXPRESSION; GENETIC TRANSFECTION; IMMUNOHISTOCHEMISTRY; INNERVATION; MOUSE; MUTATION; NERVE CELL NETWORK; NERVE ENDING; NERVE FIBER GROWTH; NEUROIMAGING; NEUROTRANSMISSION; NONHUMAN; PATHOPHYSIOLOGY; PYRAMIDAL NERVE CELL; SLICE CULTURE; SYNAPSE;

EID: 84907983473     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2014.00317     Document Type: Article

References (77)

1. Arain, F. M., Boyd, K. L., and Gallagher, M. J. (2012). Decreased viability and absence-like epilepsy in mice lacking or deficient in the GABAA receptor alpha1 subunit. Epilepsia 53, e161–e165. doi: 10.1111/j.1528-1167.2012.03596.x
2. Audenaert, D., Schwartz, E., Claeys, K. G., Claes, L., Deprez, L., Suls, A., et al. (2006). A novel GABRG2 mutation associated with febrile seizures. Neurology 67, 687–690. doi: 10.1212/01.wnl.0000230145.73496.a2
3. Baho, E., and Di Cristo, G. (2012). Neural activity and neurotransmission regulate the maturation of the innervation field of cortical GABAergic interneurons in an age-dependent manner. J. Neurosci. 32, 911–918. doi: 10.1523/JNEUROSCI.4352-11.2012
4. Baker, K. E., and Parker, R. (2004). Nonsense-mediated mRNA decay: terminating erroneous gene expression. Curr. Opin. Cell Biol. 16, 293–299. doi: 10.1016/j.ceb.2004.03.003
5. Baulac, S., Huberfeld, G., Gourfinkel-An, I., Mitropoulou, G., Beranger, A., Prud’homme, J. F., et al. (2001). First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene. Nat. Genet. 28, 46–48. doi: 10.1038/ng0501-46
6. Bernard, C. (2012). “Alterations in synaptic function in epilepsy,” in Jasper’s Basic Mechanisms of the Epilepsies, 4th edn., eds J. L. Noebels, M. Avoli, M. A. Rogawski, R. W. Olsen, and A. V. Delgado-Escueta (Bethesda, MD: Oxford University Press, Inc.), 470–483.
7. Bianchi, M. T., Song, L., Zhang, H., and Macdonald, R. L. (2002). Two different mechanisms of disinhibition produced by GABAA receptor mutations linked to epilepsy in humans. J. Neurosci. 22, 5321–5327.
8. Bosman, L. W., Heinen, K., Spijker, S., and Brussaard, A. B. (2005). Mice lacking the major adult GABAA receptor subtype have normal number of synapses, but retain juvenile IPSC kinetics until adulthood. J. Neurophysiol. 94, 338–346. doi: 10.1152/jn.00084.2005
9. Bowser, D. N., Wagner, D. A., Czajkowski, C., Cromer, B. A., Parker, M. W., Wallace, R. H., et al. (2002). Altered kinetics and benzodiazepine sensitivity of a GABAA receptor subunit mutation [gamma 2(R43Q)] found in human epilepsy. Proc. Natl. Acad. Sci. U.S.A. 99, 15170–15175. doi: 10.1073/pnas.212320199
10. Carlson, G., Wang, Y., and Alger, B. E. (2002). Endocannabinoids facilitate the induction of LTP in the hippocampus. Nat. Neurosci. 5, 723–724. doi: 10.1038/nn879
11. Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O’roak, B. J., Cook, J., et al. (2013). Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat. Genet. 45, 825–830. doi: 10.1038/ng.2646
12. Carvill, G. L., Weckhuysen, S., McMahon, J. M., Hartmann, C., Moller, R. S., Hjalgrim, H., et al. (2014). GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology 82, 1245–1253. doi: 10.1212/WNL.0000000000000291
13. Chattopadhyaya, B., Baho, E., Huang, Z. J., Schachner, M., and Di Cristo, G. (2013). Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex. J. Neurosci. 33, 5957–5968. doi: 10.1523/JNEUROSCI.1306-12.2013
14. Chattopadhyaya, B., Di Cristo, G., Higashiyama, H., Knott, G. W., Kuhlman, S. J., Welker, E., et al. (2004). Experience and activity-dependent maturation of perisomatic GABAergic innervation in primary visual cortex during a postnatal critical period. J. Neurosci. 24, 9598–9611. doi: 10.1523/JNEUROSCI.1851-04.2004
15. Chattopadhyaya, B., Di Cristo, G., Wu, C. Z., Knott, G., Kuhlman, S., Fu, Y., et al. (2007). GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex. Neuron 54, 889–903. doi: 10.1016/j.neuron.2007.05.015
16. Cossette, P., Lachance-Touchette, P., and Rouleau, G. A. (2012). “Mutated GABAA receptor subunits in idiopathic generalized epilepsy,” in Jasper’s Basic Mechanisms of the Epilepsies, 4th edn., eds J. L. Noebels, M. Avoli, M. A. Rogawski, R. W. Olsen, and A. V. Delgado-Escueta. (Bethesda, MD: Oxford University Press, Inc.), 714–730.
17. Cossette, P., Liu, L., Brisebois, K., Dong, H., Lortie, A., Vanasse, M., et al. (2002). Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat. Genet. 31, 184–189. doi: 10.1038/ng885
18. Delahanty, R. J., Kang, J. Q., Brune, C. W., Kistner, E. O., Courchesne, E., Cox, N. J., et al. (2011). Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism. Mol. Psychiatry 16, 86–96. doi: 10.1038/mp.2009.118
19. Dibbens, L. M., Feng, H. J., Richards, M. C., Harkin, L. A., Hodgson, B. L., Scott, D., et al. (2004). GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies. Hum. Mol. Genet. 13, 1315–1319. doi: 10.1093/hmg/ddh146
20. Dibbens, L. M., Harkin, L. A., Richards, M., Hodgson, B. L., Clarke, A. L., Petrou, S., et al. (2009). The role of neuronal GABA(A) receptor subunit mutations in idiopathic generalized epilepsies. Neurosci. Lett. 453, 162–165. doi: 10.1016/j.neulet.2009.02.038
21. Di Cristo, G., Chattopadhyaya, B., Kuhlman, S. J., Fu, Y., Belanger, M. C., Wu, C. Z., et al. (2007). Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plasticity. Nat. Neurosci. 10, 1569–1577. doi: 10.1038/nn2008
22. Di Cristo, G., Wu, C., Chattopadhyaya, B., Ango, F., Knott, G., Welker, E., et al. (2004). Subcellular domain-restricted GABAergic innervation in primary visual cortex in the absence of sensory and thalamic inputs. Nat. Neurosci. 7, 1184–1186. doi: 10.1038/nn1334
23. Ding, L., Feng, H. J., Macdonald, R. L., Botzolakis, E. J., Hu, N., and Gallagher, M. J. (2010). GABA(A) receptor alpha1 subunit mutation A322D associated with autosomal dominant juvenile myoclonic epilepsy reduces the expression and alters the composition of wild type GABA(A) receptors. J. Biol. Chem. 285, 26390–26405. doi: 10.1074/jbc.M110.142299
24. Dunaevsky, A., Tashiro, A., Majewska, A., Mason, C., and Yuste, R. (1999). Developmental regulation of spine motility in the mammalian central nervous system. Proc. Natl. Acad. Sci. U.S.A. 96, 13438–13443. doi: 10.1073/pnas.96.23.13438
25. Epi, K. C., Phenome, P., Allen, A. S., Berkovic, S. F., Cossette, P., Delanty, N., et al. (2013). De novo mutations in epileptic encephalopathies. Nature 501, 217–221. doi: 10.1038/nature12439
26. Eugene, E., Depienne, C., Baulac, S., Baulac, M., Fritschy, J. M., Le Guern, E., et al. (2007). GABA(A) receptor gamma 2 subunit mutations linked to human epileptic syndromes differentially affect phasic and tonic inhibition. J. Neurosci. 27, 14108–14116. doi: 10.1523/JNEUROSCI.2618-07.2007
27. Fritschy, J. M., and Panzanelli, P. (2006). Molecular and synaptic organization of GABAA receptors in the cerebellum: effects of targeted subunit gene deletions. Cerebellum 5, 275–285. doi: 10.1080/14734220600962805
28. Frugier, G., Coussen, F., Giraud, M. F., Odessa, M. F., Emerit, M. B., Boue-Grabot, E., et al. (2007). A gamma 2(R43Q) mutation, linked to epilepsy in humans, alters GABAA receptor assembly and modifies subunit composition on the cell surface. J. Biol. Chem. 282, 3819–3828. doi: 10.1074/jbc.M608910200
29. Gaiarsa, J. L., and Porcher, C. (2013). Emerging neurotrophic role of GABAB receptors in neuronal circuit development. Front. Cell. Neurosci. 7:206. doi: 10.3389/fncel.2013.00206
30. Gallagher, M. J., Ding, L., Maheshwari, A., and Macdonald, R. L. (2007). The GABAA receptor alpha1 subunit epilepsy mutation A322D inhibits transmem-brane helix formation and causes proteasomal degradation. Proc. Natl. Acad. Sci. U.S.A. 104, 12999–13004. doi: 10.1073/pnas.0700163104
31. Gallagher, M. J., Song, L., Arain, F., and Macdonald, R. L. (2004). The juvenile myoclonic epilepsy GABA(A) receptor alpha1 subunit mutation A322D produces asymmetrical, subunit position-dependent reduction of heterozygous receptor currents and alpha1 subunit protein expression. J. Neurosci. 24, 5570–5578. doi: 10.1523/JNEUROSCI.1301-04.2004
32. Goldschen-Ohm, M. P., Wagner, D. A., Petrou, S., and Jones, M. V. (2010). An epilepsy-related region in the GABA(A) receptor mediates long-distance effects on GABA and benzodiazepine binding sites. Mol. Pharmacol. 77, 35–45. doi: 10.1124/mol.109.058289
33. Gurba, K. N., Hernandez, C. C., Hu, N., and Macdonald, R. L. (2012). GABRB3 mutation, G32R, associated with childhood absence epilepsy alters alpha1beta3gamma2L gamma-aminobutyric acid type A (GABAA) receptor expression and channel gating. J. Biol. Chem. 287, 12083–12097. doi: 10.1074/jbc.M111.332528
34. Haider, B., and McCormick, D. A. (2009). Rapid neocortical dynamics: cellular and network mechanisms. Neuron 62, 171–189. doi: 10.1016/j.neuron.2009.04.008
35. Hales, T. G., Tang, H., Bollan, K. A., Johnson, S. J., King, D. P., McDonald, N. A., et al. (2005). The epilepsy mutation, gamma2(R43Q) disrupts a highly conserved inter-subunit contact site, perturbing the biogenesis of GABAA receptors. Mol. Cell. Neurosci. 29, 120–127. doi: 10.1016/j.mcn.2005.01.002
36. Hancili, S., Onal, Z. E., Ata, P., Karatoprak, E. Y., Gurbuz, T., Bostanci, M., et al. (2014). The GABAA receptor gamma2 subunit (R43Q) mutation in febrile seizures. Pediatr. Neurol. 50, 353–356. doi: 10.1016/j.pediatrneurol.2014.01.002
37. Harkin, L. A., Bowser, D. N., Dibbens, L. M., Singh, R., Phillips, F., Wallace, R. H., et al. (2002). Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus. Am. J. Hum. Genet. 70, 530–536. doi: 10.1086/338710
38. Hayama, T., Noguchi, J., Watanabe, S., Takahashi, N., Hayashi-Takagi, A., Ellis-Davies, G. C., et al. (2013). GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling. Nat. Neurosci. 16, 1409–1416. doi: 10.1038/nn.3496
39. Huang, X., Hernandez, C. C., Hu, N., and Macdonald, R. L. (2014). Three epilepsy-associated GABRG2 missense mutations at the gamma+/beta- interface disrupt GABA receptor assembly and trafficking by similar mechanisms but to different extents. Neurobiol. Dis. 68C, 167–179. doi: 10.1016/j.nbd.2014.04.015
40. Ishii, A., Kanaumi, T., Sohda, M., Misumi, Y., Zhang, B., Kakinuma, N., et al. (2014). Association of nonsense mutation in GABRG2 with abnormal trafficking of GABAA receptors in severe epilepsy. Epilepsy Res. 108, 420–432. doi: 10.1016/j.eplepsyres.2013.12.005
41. Isokawa, M. (2000). Remodeling dendritic spines of dentate granule cells in temporal lobe epilepsy patients and the rat pilocarpine model. Epilepsia 41 Suppl. 6, S14–S17. doi: 10.1111/j.1528-1157.2000.tb01550.x
42. Johnston, A. J., Kang, J. Q., Shen, W., Pickrell, W. O., Cushion, T. D., Davies, J. S., et al. (2014). A novel GABRG2 mutation, p.R136*, in a family with GEFS+ and extended phenotypes. Neurobiol. Dis. 64, 131–141. doi: 10.1016/j.nbd.2013.12.013
43. Kananura, C., Haug, K., Sander, T., Runge, U., Gu, W., Hallmann, K., et al. (2002). A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions. Arch. Neurol. 59, 1137–1141. doi: 10.1001/arch-neur.59.7.1137
44. Kang, J. Q., and Macdonald, R. L. (2004). The GABAA receptor gamma2 subunit R43Q mutation linked to childhood absence epilepsy and febrile seizures causes retention of alpha1beta2gamma2S receptors in the endoplasmic reticulum. J. Neurosci. 24, 8672–8677. doi: 10.1523/JNEUROSCI.2717-04.2004
45. Kang, J. Q., Shen, W., and Macdonald, R. L. (2006). Why does fever trigger febrile seizures? GABAA receptor gamma2 subunit mutations associated with idiopathic generalized epilepsies have temperature-dependent trafficking deficiencies. J. Neurosci. 26, 2590–2597. doi: 10.1523/JNEUROSCI.4243-05.2006
46. Kilb, W., Kirischuk, S., and Luhmann, H. J. (2013). Role of tonic GABAergic currents during pre- and early postnatal rodent development. Front. Neural Circuits 7:139. doi: 10.3389/fncir.2013.00139
47. Klassen, T., Davis, C., Goldman, A., Burgess, D., Chen, T., Wheeler, D., et al. (2011). Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. Cell 145, 1036–1048. doi: 10.1016/j.cell.2011.05.025
48. Kralic, J. E., Sidler, C., Parpan, F., Homanics, G. E., Morrow, A. L., and Fritschy, J. M. (2006). Compensatory alteration of inhibitory synaptic circuits in cerebellum and thalamus of gamma-aminobutyric acid type A receptor alpha1 subunit knockout mice. J. Comp. Neurol. 495, 408–421. doi: 10.1002/cne.20866
49. Krampfl, K., Maljevic, S., Cossette, P., Ziegler, E., Rouleau, G. A., Lerche, H., et al. (2005). Molecular analysis of the A322D mutation in the GABA receptor alpha-subunit causing juvenile myoclonic epilepsy. Eur. J. Neurosci. 22, 10–20. doi: 10.1111/j.1460-9568.2005.04168.x
50. Lachance-Touchette, P., Brown, P., Meloche, C., Kinirons, P., Lapointe, L., Lacasse, H., et al. (2011). Novel alpha1 and gamma2 GABAA receptor subunit mutations in families with idiopathic generalized epilepsy. Eur. J. Neurosci. 34, 237–249. doi: 10.1111/j.1460-9568.2011.07767.x
51. Lachance-Touchette, P., Martin, C., Poulin, C., Gravel, M., Carmant, L., and Cossette, P. (2010). Screening of GABRB3 in French-Canadian families with idiopathic generalized epilepsy. Epilepsia 51, 1894–1897. doi: 10.1111/j.1528-1167.2010.02642.x
52. Lee, K. F., Soares, C., and Beique, J. C. (2012). Examining form and function of dendritic spines. Neural Plast. 2012:704103. doi: 10.1155/2012/704103
53. Li, M. Z., and Elledge, S. J. (2007). Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC. Nat. Methods 4, 251–256. doi: 10.1038/nmeth1010
54. Liu, Q. S., Pu, L., and Poo, M. M. (2005). Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons. Nature 437, 1027–1031. doi: 10.1038/nature04050
55. Luscher, C., Nicoll, R. A., Malenka, R. C., and Muller, D. (2000). Synaptic plasticity and dynamic modulation of the postsynaptic membrane. Nat. Neurosci. 3, 545–550. doi: 10.1038/75714
56. Ma, Y., Ramachandran, A., Ford, N., Parada, I., and Prince, D. A. (2013). Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy. Epilepsia 54, 1232–1239. doi: 10.1111/epi.12195
57. Macdonald, R. L., and Kang, J. Q. (2009). Molecular pathology of genetic epilepsies associated with GABAA receptor subunit mutations. Epilepsy Curr. 9, 18–23. doi: 10.1111/j.1535-7511.2008.01278.x
58. Macdonald, R. L., Kang, J. Q., and Gallagher, M. J. (2010). Mutations in GABAA receptor subunits associated with genetic epilepsies. J. Physiol. 588, 1861–1869. doi: 10.1113/jphysiol.2010.186999
59. Maljevic, S., Krampfl, K., Cobilanschi, J., Tilgen, N., Beyer, S., Weber, Y. G., et al. (2006). A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy. Ann. Neurol. 59, 983–987. doi: 10.1002/ana.20874
60. Multani, P., Myers, R. H., Blume, H. W., Schomer, D. L., and Sotrel, A. (1994). Neocortical dendritic pathology in human partial epilepsy: a quantitative Golgi study. Epilepsia 35, 728–736. doi: 10.1111/j.1528-1157.1994.tb02503.x
61. Queenan, B. N., Lee, K. J., and Pak, D. T. (2012). Wherefore art thou, homeo(stasis)? Functional diversity in homeostatic synaptic plasticity. Neural Plast 2012:718203. doi: 10.1155/2012/718203
62. Rossignol, E. (2011). Genetics and function of neocortical GABAergic interneu-rons in neurodevelopmental disorders. Neural Plast. 2011:649325. doi: 10.1155/2011/649325
63. Shi, X., Huang, M. C., Ishii, A., Yoshida, S., Okada, M., Morita, K., et al. (2010). Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies. J. Hum. Genet. 55, 375–378. doi: 10.1038/jhg.2010.47
64. Sieghart, W., and Sperk, G. (2002). Subunit composition, distribution and function of GABA(A) receptor subtypes. Curr. Top. Med. Chem. 2, 795–816. doi: 10.2174/1568026023393507
65. Stoppini, L., Buchs, P. A., and Muller, D. (1991). A simple method for organotypic cultures of nervous tissue. J. Neurosci. Methods 37, 173–182. doi: 10.1016/0165-0270(91)90128-M
66. Sun, H., Zhang, Y., Liang, J., Liu, X., Ma, X., Wu, H., et al. (2008). SCN1A, SCN1B, and GABRG2 gene mutation analysis in Chinese families with generalized epilepsy with febrile seizures plus. J. Hum. Genet. 53, 769–774. doi: 10.1007/s10038-008-0306-y
67. Tan, H. O., Reid, C. A., Single, F. N., Davies, P. J., Chiu, C., Murphy, S., et al. (2007). Reduced cortical inhibition in a mouse model of familial childhood absence epilepsy. Proc. Natl. Acad. Sci. U.S.A. 104, 17536–17541. doi: 10.1073/pnas.0708440104
68. Tanaka, M., Olsen, R. W., Medina, M. T., Schwartz, E., Alonso, M. E., Duron, R. M., et al. (2008). Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy. Am. J. Hum. Genet. 82, 1249–1261. doi: 10.1016/j.ajhg.2008.04.020
69. Tian, M., Mei, D., Freri, E., Hernandez, C. C., Granata, T., Shen, W., et al. (2013). Impaired surface alphabetagamma GABA(A) receptor expression in familial epilepsy due to a GABRG2 frameshift mutation. Neurobiol. Dis. 50, 135–141. doi: 10.1016/j.nbd.2012.10.008
70. Todd, E., Gurba, K. N., Botzolakis, E. J., Stanic, A. K., and Macdonald, R. L. (2014). GABAA receptor biogenesis is impaired by the gamma2 subunit febrile seizure-associated mutation, GABRG2(R177G). Neurobiol. Dis. 69, 215–224. doi: 10.1016/j.nbd.2014.05.013
71. Trevelyan, A. J., Baldeweg, T., Van Drongelen, W., Yuste, R., and Whittington, M. (2007). The source of afterdischarge activity in neocortical tonic-clonic epilepsy. J. Neurosci. 27, 13513–13519. doi: 10.1523/JNEUROSCI.3005-07.2007
72. Vicini, S., Ferguson, C., Prybylowski, K., Kralic, J., Morrow, A. L., and Homanics, G. E. (2001). GABA(A) receptor alpha1 subunit deletion prevents developmental changes of inhibitory synaptic currents in cerebellar neurons. J. Neurosci. 21, 3009–3016.
73. Wallace, R. H., Marini, C., Petrou, S., Harkin, L. A., Bowser, D. N., Panchal, R. G., et al. (2001). Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures. Nat. Genet. 28, 49–52. doi: 10.1038/ng0501-49
74. Whissell, P. D., Eng, D., Lecker, I., Martin, L. J., Wang, D. S., and Orser, B. A. (2013). Acutely increasing deltaGABA(A) receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus. Front. Neural Circuits 7:146. doi: 10.3389/fncir.2013.00146
75. Wong, M. (2005). Modulation of dendritic spines in epilepsy: cellular mechanisms and functional implications. Epilepsy Behav. 7, 569–577. doi: 10.1016/j.yebeh.2005.08.007
76. Wu, X., Fu, Y., Knott, G., Lu, J., Di Cristo, G., and Huang, Z. J. (2012). GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons. J. Neurosci. 32, 331–343. doi: 10.1523/JNEUROSCI.3189-11.2012
77. Zeller, A., Jurd, R., Lambert, S., Arras, M., Drexler, B., Grashoff, C., et al. (2008). Inhibitory ligand-gated ion channels as substrates for general anesthetic actions. Handb. Exp. Pharmacol. 182, 31–51. doi: 10.1007/978-3-540-74806-9_2