GABAa receptor α and γ subunits shape synaptic currents via different mechanisms

Journal of Biological Chemistry

Volumn 289, Issue 9, 2014, Pages 5399-5411

  Dixon, Christine ^a   Sah, Pankaj ^a   Lynch, Joseph W ^a   Keramidas, Angelo ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

BURST DURATION; DEACTIVATION RATE; DIFFERENT MECHANISMS; INTRACELLULAR DOMAIN; KINETIC PROPERTIES; SINGLE CHANNEL RECORDING; SINGLE-CHANNEL ANALYSIS; SYNAPTIC TRANSMISSION;

BIOCHEMISTRY; BIOLOGY;

CHEMICAL REACTIONS;

4 AMINOBUTYRIC ACID A RECEPTOR ALPHA1; 4 AMINOBUTYRIC ACID A RECEPTOR ALPHA2; 4 AMINOBUTYRIC ACID A RECEPTOR GAMMA1; 4 AMINOBUTYRIC ACID A RECEPTOR GAMMA2; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID A RECEPTOR STIMULATING AGENT; CHLORIDE CHANNEL;

AMINO TERMINAL SEQUENCE; AMYGDALOID NUCLEUS; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BINDING SITE; BRAIN NERVE CELL; BRAIN REGION; CELL TRANSFER; COMPLEX FORMATION; CONTROLLED STUDY; ELECTROENCEPHALOGRAM; EMBRYO; GABAERGIC TRANSMISSION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; RAT; SYNAPSE; SYNAPTIC TRANSMISSION; ANIMAL; CELL STRAIN HEK293; CYS-LOOP RECEPTORS; DRUG POTENTIATION; GABA RECEPTORS; GENETICS; HUMAN; KINETICS; METABOLISM; PHYSIOLOGY; PROTEIN SUBUNIT;

CHLORIDE CHANNELS; CYS-LOOP RECEPTORS; GABA RECEPTORS; KINETICS; SYNAPSES;

ANIMALS; GABA-A RECEPTOR AGONISTS; HEK293 CELLS; HUMANS; PROTEIN SUBUNITS; RATS; RECEPTORS, GABA-A; SYNAPSES; SYNAPTIC TRANSMISSION;

EID: 84896874039     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.514695     Document Type: Article

References (59)

1. Olsen, R. W., and Sieghart, W. (2008) International Union of Pharmacology. LXX. Subtypes of γ-aminobutyric acid(A) receptors. Classification on the basis of subunit composition, pharmacology, and function. Update. Pharmacol. Rev. 60, 243-260
2. Pirker, S., Schwarzer, C., Wieselthaler, A., Sieghart, W., and Sperk, G. (2000) GABA(A) receptors. Immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience 101, 815-850
3. Schofield, C. M., and Huguenard, J. R. (2007) GABA affinity shapes IPSCs in thalamic nuclei. J. Neurosci. 27, 7954-7962 (Pubitemid 47173308)
4. Eyre, M. D., Renzi, M., Farrant, M., and Nusser, Z. (2012) Setting the time course of inhibitory synaptic currents by mixing multiple GABA(A) receptor α subunit isoforms. J. Neurosci. 32, 5853-5867
5. Kneussel, M., Brandstätter, J. H., Gasnier, B., Feng, G., Sanes, J. R., and Betz, H. (2001) Gephyrin-independent clustering of postsynaptic GABA(A) receptor subtypes. Mol. Cell. Neurosci. 17, 973-982 (Pubitemid 32641867)
6. Körber, C., Richter, A., Kaiser, M., Schlicksupp, A., Mükusch, S., Kuner, T., Kirsch, J., and Kuhse, J. (2012) Effects of distinct collybistin isoforms on the formation of GABAergic synapses in hippocampal neurons. Mol. Cell. Neurosci. 50, 250-259
7. Keramidas, A., and Harrison, N. L. (2010) The activation mechanism of α1β2γ2S and α3β3γ2S GABAA receptors. J. Gen. Physiol. 135, 59-75
8. Lavoie, A. M., Tingey, J. J., Harrison, N. L., Pritchett, D. B., and Twyman, R. E. (1997) Activation and deactivation rates of recombinant GABA(A) receptor channels are dependent on α-subunit isoform. Biophys. J. 73, 2518-2526 (Pubitemid 27471460)
9. Okada, M., Onodera, K., Van Renterghem, C., Sieghart, W., and Takahashi, T. (2000) Functional correlation of GABA(A) receptor α subunits expression with the properties of IPSCs in the developing thalamus. J. Neurosci. 20, 2202-2208 (Pubitemid 30230073)
10. Essrich, C., Lorez, M., Benson, J. A., Fritschy, J. M., and Lüscher, B. (1998) Postsynaptic clustering of major GABAA receptor subtypes requires the γ2 subunit and gephyrin. Nat. Neurosci. 1, 563-571
11. Fritschy, J. M., Harvey, R. J., and Schwarz, G. (2008) Gephyrin. Where do we stand, where do we go? Trends Neurosci. 31, 257-264
12. Alldred, M. J., Mulder-Rosi, J., Lingenfelter, S. E., Chen, G., and Lüscher, B. (2005) Distinct γ2 subunit domains mediate clustering and synaptic function of postsynaptic GABAA receptors and gephyrin. J. Neurosci. 25, 594-603
13. Kowalczyk, S., Winkelmann, A., Smolinsky, B., Förstera, B., Neundorf, I., Schwarz, G., and Meier, J. C. (2013) Direct binding of GABAA receptor β2 and β3 subunits to gephyrin. Eur. J. Neurosci. 37, 544-554
14. Saiepour, L., Fuchs, C., Patrizi, A., Sassoè-Pognetto, M., Harvey, R. J., and Harvey, K. (2010) Complex role of collybistin and gephyrin in GABAA receptor clustering. J. Biol. Chem. 285, 29623-29631
15. Panzanelli, P., Gunn, B. G., Schlatter, M. C., Benke, D., Tyagarajan, S. K., Scheiffele, P., Belelli, D., Lambert, J. J., Rudolph, U., and Fritschy, J. M. (2011) Distinct mechanisms regulate GABAA receptor and gephyrin clustering at perisomatic and axo-axonic synapses on CA1 pyramidal cells. J. Physiol. 589, 4959-4980
16. Günther, U., Benson, J., Benke, D., Fritschy, J. M., Reyes, G., Knoflach, F., Crestani, F., Aguzzi, A., Arigoni, M., and Lang, Y. (1995) Benzodiazepine-insensitive mice generated by targeted disruption of the γ2 subunit gene of γ-aminobutyric acid type A receptors. Proc. Natl. Acad. Sci. U.S.A. 92, 7749-7753
17. Möhler, H., Crestani, F., and Rudolph, U. (2001) GABA(A)-receptor subtypes. A new pharmacology. Curr. Opin. Pharmacol. 1, 22-25
18. Esmaeili, A., Lynch, J. W., and Sah, P. (2009) GABAA receptors containing γ1 subunits contribute to inhibitory transmission in the central amygdala. J. Neurophysiol. 101, 341-349
19. A/benzodiazepine receptors. EMBO J. 9, 3261-3267
20. Nusser, Z., Cull-Candy, S., and Farrant, M. (1997) Differences in synaptic GABA(A) receptor number underlie variation in GABA mini amplitude. Neuron 19, 697-709 (Pubitemid 27430755)
21. Wafford, K. A., Whiting, P. J., and Kemp, J. A. (1993) Differences in affinity and efficacy of benzodiazepine receptor ligands at recombinant γ-aminobutyric acidA receptor subtypes. Mol. Pharmacol. 43, 240-244 (Pubitemid 23055068)
22. Chih, B., Gollan, L., and Scheiffele, P. (2006) Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex. Neuron 51, 171-178 (Pubitemid 44063616)
23. Brewer, G. J. (1995) Serum-free B27/neurobasal medium supports differentiated growth of neurons from the striatum, substantia nigra, septum, cerebral cortex, cerebellum, and dentate gyrus. J. Neurosci. Res. 42, 674-683
24. Barry, P. H. (1994) JPCalc, a software package for calculating liquid junction potential corrections in patch-clamp, intracellular, epithelial and bilayer measurements and for correcting junction potential measurements. J. Neurosci. Methods 51, 107-116
25. Lema, G. M., and Auerbach, A. (2006) Modes and models of GABA(A) receptor gating. J. Physiol. 572, 183-200
26. Colquhoun, D., and Sigworth, F. J. (1995) Fitting and statistical analysis of single-channel records. In Single-Channel Recordings, 2 Ed., pp. 483-585, Plenum Press, New York
27. Qin, F., Auerbach, A., and Sachs, F. (1997) Maximum likelihood estimation of aggregated Markov processes. Proc. Biol. Sci. 264, 375-383 (Pubitemid 27144045)
28. Angelotti, T. P., and Macdonald, R. L. (1993) Assembly of GABAA receptor subunits. α1β1 and α1β1γ 2S subunits produce unique ion channels with dissimilar single-channel properties. J. Neurosci. 13, 1429-1440 (Pubitemid 23095388)
29. Lorez, M., Benke, D., Luscher, B., Mohler, H., and Benson, J. A. (2000) Single-channel properties of neuronal GABAA receptors from mice lacking the 2 subunit. J. Physiol. 527, 11-31 (Pubitemid 30649581)
30. Keramidas, A., and Harrison, N. L. (2008) Agonist-dependent single channel current and gating in α4β2δ and α1β2γ 2S GABAA receptors. J. Gen. Physiol. 131, 163-181
31. Keramidas, A., Kash, T. L., and Harrison, N. L. (2006) The pre-M1 segment of the α1 subunit is a transduction element in the activation of the GABAA receptor. J. Physiol. 575, 11-22 (Pubitemid 44178126)
32. McClellan, A. M., and Twyman, R. E. (1999) Receptor system response kinetics reveal functional subtypes of native murine and recombinant human GABAA receptors. J. Physiol. 515, 711-727 (Pubitemid 29140107)
33. Wyllie, D. J., Behe, P., and Colquhoun, D. (1998) Single-channel activations and concentration jumps. Comparison of recombinant NR1a/NR2A and NR1a/NR2D NMDA receptors. J. Physiol. 510, 1-18 (Pubitemid 28351920)
34. Elenes, S., Ni, Y., Cymes, G. D., and Grosman, C. (2006) Desensitization contributes to the synaptic response of gain-of-function mutants of the muscle nicotinic receptor. J. Gen. Physiol. 128, 615-627 (Pubitemid 44664638)
35. Sine, S. M., and Engel, A. G. (2006) Recent advances in Cys-loop receptor structure and function. Nature 440, 448-455
36. Jones, M. V., and Westbrook, G. L. (1995) Desensitized states prolong GABAA channel responses to brief agonist pulses. Neuron 15, 181-191
37. Maric, H. M., Mukherjee, J., Tretter, V., Moss, S. J., and Schindelin, H. (2011) Gephyrin-mediated γ-aminobutyric acid type A and glycine receptor clustering relies on a common binding site. J. Biol. Chem. 286, 42105-42114
38. Wu, X., Wu, Z., Ning, G., Guo, Y., Ali, R., Macdonald, R. L., De Blas, A. L., Luscher, B., and Chen, G. (2012) γ-Aminobutyric acid type A (GABAA) receptor α subunits play a direct role in synaptic versus extrasynaptic targeting. J. Biol. Chem. 287, 27417-27430
39. Tretter, V., Jacob, T. C., Mukherjee, J., Fritschy, J. M., Pangalos, M. N., and Moss, S. J. (2008) The clustering of GABA(A) receptor subtypes at inhibitory synapses is facilitated via the direct binding of receptor α2 subunits to gephyrin. J. Neurosci. 28, 1356-1365 (Pubitemid 351231519)
40. Lévi, S., Logan, S. M., Tovar, K. R., and Craig, A. M. (2004) Gephyrin is critical for glycine receptor clustering but not for the formation of functional GABAergic synapses in hippocampal neurons. J. Neurosci. 24, 207-217 (Pubitemid 38181685)
41. Colquhoun, D. (1998) Binding, gating, affinity and efficacy. The interpretation of structure-activity relationships for agonists and of the effects of mutating receptors. Br. J. Pharmacol. 125, 924-947
42. Lape, R., Colquhoun, D., and Sivilotti, L. G. (2008) On the nature of partial agonism in the nicotinic receptor superfamily. Nature 454, 722-727
43. Mukhtasimova, N., Lee, W. Y., Wang, H. L., and Sine, S. M. (2009) Detection and trapping of intermediate states priming nicotinic receptor channel opening. Nature 459, 451-454
44. Jadey, S., and Auerbach, A. (2012) An integrated catch-and-hold mechanism activates nicotinic acetylcholine receptors. J. Gen. Physiol. 140, 17-28
45. Krashia, P., Lape, R., Lodesani, F., Colquhoun, D., and Sivilotti, L. G. (2011) The long activations of α2 glycine channels can be described by a mechanism with reaction intermediates ("flip"). J. Gen. Physiol. 137, 197-216
46. Lape, R., Plested, A. J., Moroni, M., Colquhoun, D., and Sivilotti, L. G. (2012) The α1K276E startle disease mutation reveals multiple intermediate states in the gating of glycine receptors. J. Neurosci. 32, 1336-1352
47. Gielen, M. C., Lumb, M. J., and Smart, T. G. (2012) Benzodiazepines modulate GABAA receptors by regulating the preactivation step after GABA binding. J. Neurosci. 32, 5707-5715
48. Dong, N., Qi, J., and Chen, G. (2007) Molecular reconstitution of functional GABAergic synapses with expression of neuroligin-2 and GABAA receptors. Mol. Cell. Neurosci. 35, 14-23 (Pubitemid 46636296)
49. Wingrove, P. B., Thompson, S. A., Wafford, K. A., and Whiting, P. J. (1997) Key amino acids in the γ subunit of the γ-aminobutyric acid A receptor that determine ligand binding and modulation at the benzodiazepine site. Mol. Pharmacol. 52, 874-881 (Pubitemid 27484180)
50. Buhr, A., and Sigel, E. (1997) A point mutation in the γ2 subunit of γ-aminobutyric acid type A receptors results in altered benzodiazepine binding site specificity. Proc. Natl. Acad. Sci. U.S.A. 94, 8824-8829 (Pubitemid 27335124)
51. Buhr, A., Baur, R., and Sigel, E. (1997) Subtle changes in residue 77 of the γ subunit of α1β2γ2 GABA A receptors drastically alter the affinity for ligands of the benzodiazepine binding site. J. Biol. Chem. 272, 11799-11804 (Pubitemid 27202747)
52. Hanson, S. M., and Czajkowski, C. (2008) Structural mechanisms underlying benzodiazepine modulation of the GABA(A) receptor. J. Neurosci. 28, 3490-3499 (Pubitemid 351469312)
53. Delaney, A. J., and Sah, P. (2001) Pathway-specific targeting of GABA(A) receptor subtypes to somatic and dendritic synapses in the central amygdala. J. Neurophysiol. 86, 717-723 (Pubitemid 32738562)
54. Loebrich, S., Bähring, R., Katsuno, T., Tsukita, S., and Kneussel, M. (2006) Activated radixin is essential for GABA(A) receptor α5 subunit anchoring at the actin cytoskeleton. EMBO J. 25, 987-999 (Pubitemid 43372113)
55. Thomson, A. M., and Jovanovic, J. N. (2010) Mechanisms underlying synapse-specific clustering of GABA(A) receptors. Eur. J. Neurosci. 31, 2193-2203
56. Ribrault, C., Sekimoto, K., and Triller, A. (2011) From the stochasticity of molecular processes to the variability of synaptic transmission. Nat. Rev. Neurosci. 12, 375-387
57. A receptors to synaptic and extrasynaptic membranes of cerebellar granule cells. J. Neurosci. 18, 1693-1703
58. Bannai, H., Lévi, S., Schweizer, C., Inoue, T., Launey, T., Racine, V., Sibarita, J. B., Mikoshiba, K., and Triller, A. (2009) Activity-dependent tuning of inhibitory neurotransmission based on GABAAR diffusion dynamics. Neuron 62, 670-682
59. Crestani, F., Lorez, M., Baer, K., Essrich, C., Benke, D., Laurent, J. P., Belzung, C., Fritschy, J. M., Lüscher, B., and Mohler, H. (1999) Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues. Nat. Neurosci. 2, 833-839 (Pubitemid 30491177)