Nicotinic acetylcholine receptors at the single-channel level

British Journal of Pharmacology

Volumn 175, Issue 11, 2018, Pages 1789-1804

  Bouzat, Cecilia ^a   Sine, Steven M ^b,c  

^a UNIVERSIDAD NACIONAL DEL SUR   (Argentina)

^b MAYO GRADUATE SCHOOL   (United States)

^c Mayo Clinic College of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCHOLINE; BUNGAROTOXIN RECEPTOR; ION CHANNEL; LIGAND; NEUROTRANSMITTER; NICOTINIC RECEPTOR; RECEPTOR SUBTYPE; NICOTINIC RECEPTOR BLOCKING AGENT;

ACETYLCHOLINE RELEASE; AWARDS AND PRIZES; DRUG TARGETING; EXCITATION; HUMAN; MEDICAL RESEARCH; MUSCLE; NERVE; NONHUMAN; PATCH CLAMP TECHNIQUE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; RECEPTOR BINDING; REVIEW; STOICHIOMETRY; ANIMAL; BINDING SITE; DRUG EFFECT; METABOLISM; MOLECULAR MODEL;

ANIMALS; BINDING SITES; HUMANS; MODELS, MOLECULAR; NICOTINIC ANTAGONISTS; PATCH-CLAMP TECHNIQUES; RECEPTORS, NICOTINIC;

EID: 85017449622     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.13770     Document Type: Review

References (160)

1. Akk G, Steinbach JH (2005). Galantamine activates muscle-type nicotinic acetylcholine receptors without binding to the acetylcholine-binding site. J Neurosci 25: 1992–2001.
2. Alexander SPH, Peters JA, Kelly E, Marrion N, Benson HE, Faccenda E et al. (2015). The Concise Guide to PHARMACOLOGY 2015/16: Ligand-gated ion channels. Br J Pharmacol 172: 5870–5903.
3. Amador M, Dani JA (1991). MK-801 inhibition of nicotinic acetylcholine receptor channels. Synapse 7: 207–215.
4. Andersen N, Corradi J, Bartos M, Sine SM, Bouzat C (2011). Functional relationships between agonist binding sites and coupling regions of homomeric Cys-loop receptors. J Neurosci 31: 3662–3669.
5. Andersen N, Corradi J, Sine SM, Bouzat C (2013). Stoichiometry for activation of neuronal α7 nicotinic receptors. Proc Natl Acad Sci U S A 110: 20819–20824.
6. Andersen ND, Nielsen BE, Corradi J, Tolosa MF, Feuerbach D, Arias HR et al. (2016). Exploring the positive allosteric modulation of human α7 nicotinic receptors from a single-channel perspective. Neuropharmacology 107: 189–200.
7. Antollini SS, Barrantes FJ (1998). Disclosure of discrete sites for phospholipid and sterols at the protein–lipid interface in native acetylcholine receptor-rich membrane. Biochemistry 37: 16653–16662.
8. Antollini SS, Barrantes FJ (2016). Fatty acid regulation of voltage- and ligand-gated ion channel function. Front Physiol 7: 573.
9. Baenziger JE, Hénault CM, Therien JP, Sun J (2015). Nicotinic acetylcholine receptor-lipid interactions: mechanistic insight and biological function. Biochim Biophys Acta 1848: 1806–1817.
10. Barrantes FJ (2015). Phylogenetic conservation of protein-lipid motifs in pentameric ligand-gated ion channels. Biochim Biophys Acta 1848: 1796–1805.
11. Bartos M, Corradi J, Bouzat C (2009). Structural basis of activation of cys-loop receptors: the extracellular-transmembrane interface as a coupling region. Mol Neurobiol 40: 236–252.
12. Bertrand D, Gopalakrishnan M (2007). Allosteric modulation of nicotinic acetylcholine receptors. Biochem Pharmacol 74: 1155–1163.
13. Bertrand D, Bertrand S, Cassar S, Gubbins E, Li J, Gopalakrishnan M (2008). Positive allosteric modulation of the α7 nicotinic acetylcholine receptor: ligand interactions with distinct binding sites and evidence for a prominent role of the M2-M3 segment. Mol Pharmacol 74: 1407–1416.
14. Blatz AL, Magleby KL (1986). Correcting single channel data for missed events. Biophys J 49: 967–980.
15. Bocquet N, Nury H, Baaden M, Le Poupon C, Changeux JP, Delarue M et al. (2009). X-ray structure of a pentameric ligand gated ion channel in an apparently open conformation. Nature 457: 111–114.
16. Bouzat C (1996). Ephedrine blocks wild-type and long-lived mutant acetylcholine receptor channels. Neuroreport 8: 317–321.
17. Bouzat CB, Barrantes FJ (1993). Effects of long-chain fatty acids on the channel activity of the nicotinic acetylcholine receptor. Receptors Channels 1: 251–258.
18. Bouzat CB, Barrantes FJ (1996). Modulation of muscle nicotinic acetylcholine receptors by the glucocorticoid hydrocortisone. Possible allosteric mechanism of channel blockade. J Biol Chem 271: 25835–25841.
19. Bouzat C, Bren N, Sine SM (1994). Structural basis of the different gating kinetics of fetal and adult acetylcholine receptors. Neuron 13: 1395–1402.
20. Bouzat C, Roccamo AM, Garbus I, Barrantes FJ (1998). Mutations at lipid-exposed residues of the acetylcholine receptor affect its gating kinetics. Mol Pharmacol 54: 146–153.
21. Bouzat C, Barrantes FJ, Sine S (2000). Nicotinic receptor fourth transmembrane domain: hydrogen bonding by conserved threonine contributes to channel gating kinetics. J Gen Physiol 115: 663–672.
22. Bouzat C, Gumilar F, Spitzmaul G, Wang HL, Rayes D, Hansen SB et al. (2004). Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel. Nature 430: 896–900.
23. Bouzat C, Bartos M, Corradi J, Sine SM (2008). The interface between extracellular and transmembrane domains of homomeric Cys-loop receptors governs open-channel lifetime and rate of desensitization. J Neurosci 28: 7808–7819.
24. Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van Der Oost J, Smit AB et al. (2001). Crystal structure of an ACh-binding protein reveals the ligand binding domain of nicotinic receptors. Nature 411: 269–276.
25. Burzomato V, Beato M, Groot-Kormelink PJ, Colquhoun D, Sivilotti LG (2004). Single-channel behavior of heteromeric alpha1beta glycine receptors: an attempt to detect a conformational change before the channel opens. J Neurosci 24: 10924–10940.
26. Carbone L, Moroni M, Groot-Kormelink PJ, Bermudez I (2009). Pentameric concatenated (alpha4)(2)(beta2)(3) and (alpha4)(3)(beta2)(2) nicotinic acetylcholine receptors: subunit arrangement determines functional expression. Br J Pharmacol 156: 970–981.
27. Changeux JP, Taly A (2008). Nicotinic receptors, allosteric proteins and medicine. Trends Mol Med 14: 93–102.
28. Changeux JP, Pinset C, Ribera AB (1986). Effects of chlorpromazine and phencyclidine on mouse C2 acetylcholine receptor kinetics. J Physiol 378: 497–513.
29. Claudio T, Green W, Hartman D, Hayden D, Paulson HL, Sigworth FJ et al. (1987). Genetic reconstitution of functional acetylcholine receptor channels in mouse fibroblasts. Science 238: 1688–1694.
30. Collins T, Millar NS (2010). Nicotinic acetylcholine receptor transmembrane mutations convert ivermectin from a positive to a negative allosteric modulator. Mol Pharmacol 78: 198–204.
31. Colquhoun D, Hawkes A (1981). On the stochastic properties of single ion channels. Proc R Soc Lond B Biol Sci 211: 205–235.
32. Colquhoun D, Sakmann B (1981). Fluctuations in the microsecond time range of the current through single acetylcholine receptor ion channels. Nature 294: 464–466.
33. Colquhoun D, Sakmann B (1985). Fast events in single channel currents activated by acetylcholine and its analogs at the frog muscle endplate. J Physiol 369: 501–557.
34. Colquhoun D, Sigworth FJ (1983). Fitting and statistical analysis of single-channel records. In: Sakmann B, Neher E (eds). Single-Channel Recording, 1st edn. Plenum Press: NY.
35. 3 A receptors. J Neurosci 34: 16865–16876.
36. Corradi J, Bouzat C (2016). Understanding the bases of function and modulation of α7 nicotinic receptors: implications for drug discovery. Mol Pharmacol 90: 288–299.
37. Crouzy SC, Sigworth FJ (1990). Yet another approach to the dwell-time omission problem of single channel analysis. Biophys J 58: 731–743.
38. Curtis L, Buisson B, Bertrand S, Bertrand D (2002). Potentiation of human alpha4beta2 neuronal nicotinic acetylcholine receptor by estradiol. Mol Pharmacol 61: 127–135.
39. daCosta CJB, Sine SM (2013). Stoichiometry for drug potentiation of a pentameric ion channel. Proc Natl Acad Sci U S A 110: 6595–6600.
40. daCosta CJB, Free CR, Corradi J, Bouzat C, Sine SM (2011). Single-channel and structural foundations of neuronal α7 acetylcholine receptor potentiation. J Neurosci 31: 13870–13879.
41. daCosta CJB, Free CR, Sine SM (2015). Stoichiometry for α-bungarotoxin block of α7 acetylcholine receptors. Nat Commun 6: 8057. https://doi.org/10.1038/ncomms9057.
42. del Castillo J, Katz B (1957). Interaction at end-plate receptors of different choline derivatives. Proc R Soc Lond B Biol Sci 146: 369–381.
43. Dilger JP, Brett RS, Lesko LA (1991). Effects of isoflurane on acetylcholine receptor channels. 1. Single-channel currents. Mol Pharmacol 41: 127–133.
44. Dionne VE, Steinbach JH, Stevens CF (1978). An analysis of the dose-response relationship at voltage-clamped frog neuromuscular junctions. J Physiol 281: 421–444.
45. Du J, Lu W, Wu S, Cheng Y, Gouaux E (2015). Glycine receptor mechanism elucidated by electron cryo-microscopy. Nature 526: 224–229.
46. Edelstein SJ, Schaad O, Henry H, Bertrand D, Changeux JP (1996). A kinetic mechanism for nicotinic acetylcholine receptors based on multiple allosteric transitions. Biol Cybern 75: 361–379.
47. Egea J, Buendia I, Parada E, Navarro E, León R, Lopez MG (2015). Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection. Biochem Pharmacol 97: 463–472.
48. Engel AG (2007). The therapy of congenital myasthenic syndromes. Neurotherapeutics 4: 252–257.
49. Fersht AR, Leatherbarrow RJ, Wells TNC (1986). Quantitative analysis of structure-activity relationships in engineered proteins by linear free-energy relationships. Nature 322: 284–286.
50. Forman SA, Zhou Q (1999). Novel modulation of a nicotinic receptor channel mutant reveals that the open state is stabilized by ethanol. Mol Pharmacol 55: 102–108.
51. Forman SA, Chiara DC, Miller KW (2015). Anesthetics target interfacial transmembrane sites in nicotinic acetylcholine receptors. Neuropharmacology 96: 169–177.
52. Fukudome T, Ohno K, Brengman JM, Engel AG (1998). AChR channel blockade by quinidine sulfate reduces channel open duration in the slow-channel congenital myasthenic syndrome. Ann N Y Acad Sci 841: 199–202.
53. Gill JK, Savolainen M, Young GT, Zwart R, Sher E, Millar NS (2011). Agonist activation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site. Proc Natl Acad Sci U S A 108: 5867–5872.
54. Gill J, Dhankher P, Sheppard T, Sher E, Millar N (2012). A series of α7 nicotinic acetylcholine receptor allosteric modulators with close chemical similarity but diverse pharmacological properties. Mol Pharmacol 81: 710–718.
55. Gill JK, Chatzidaki A, Ursu D, Sher E, Millar NS (2013). Contrasting properties of α7-selective orthosteric and allosteric agonists examined on native nicotinic acetylcholine receptors. PLoS One 8: e55047. https://doi.org/10.1371/journal.pone.0055047.
56. Gill-Thind JK, Dhankher P, D'Oyley JM, Sheppard TD, Millar NS (2015). Structurally similar allosteric modulators of α7 nicotinic acetylcholine receptors exhibit five distinct pharmacological effects. J Biol Chem 290: 3552–3562.
57. Grønlien JH, Håkerud M, Ween H, Thorin-Hagene K, Briggs CA, Gopalakrishnan M et al. (2007). Distinct profiles of alpha7 nAChR positive allosteric modulation revealed by structurally diverse chemotypes. Mol Pharmacol 72: 715–724.
58. Grosman C, Zhou M, Auerbach A (2000). Mapping the conformational wave of acetylcholine receptor channel gating. Nature 403: 773–776.
59. Guerra-Álvarez M, Moreno-Ortega AJ, Navarro E, Fernández-Morales JC, Egea J, López MG et al. (2015). Positive allosteric modulation of alpha-7 nicotinic receptors promotes cell death by inducing Ca2+ release from the endoplasmic reticulum. J Neurochem 133: 309–319.
60. Gumilar F, Arias HR, Spitzmaul G, Bouzat C (2003). Molecular mechanisms of inhibition of nicotinic acetylcholine receptors by tricyclic antidepressants. Neuropharmacology 45: 964–976.
61. Gupta S, Auerbach A (2011). Temperature dependence of acetylcholine receptor channels activated by different agonists. Biophys J 100: 895–903.
62. Gupta S, Chakraborty S, Vij R, Auerbach A (2017). A mechanism for acetylcholine receptor gating based on structure, coupling, phi and flip. J Gen Physiol 149: 85–103.
63. Gurney AM, Rang HP (1984). The channel-blocking action of methonium compounds on rat submandibular ganglion cells. Br J Pharmacol 82: 623–642.
64. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981). Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391: 85–100.
65. Hansen SB, Taylor P (2007). Galanthamine and non-competitive inhibitor binding to ACh-binding protein: evidence for a binding site on non-alpha-subunit interfaces of heteromeric neuronal nicotinic receptors. J Mol Biol 369: 895–901.
66. Harper CM, Fukodome T, Engel AG (2003). Treatment of slow-channel congenital myasthenic syndrome with fluoxetine. Neurology 60: 1710–1713.
67. 3 receptor. Nature 512: 276–281.
68. Haung X, Chen H, Michelson K, Schneider S, Shaffer PL (2015). Crystal structure of human glycine receptor-a3 bound to antagonist strychnine. Nature 526: 277–280.
69. Hawkes AG, Jalali A, Colquhoun D (1990). The distributions of the apparent open times and shut times in a single channel record when brief events cannot be detected. Philos Trans R Soc Lond A 332: 511–538.
70. Herlitze S, Villarroel A, Witzemann V, Koenen M, Sakmann B (1996). Structural determinants of channel conductance in fetal and adult rat muscle acetylcholine receptors. J Physiol 492: 775–787.
71. Hibbs RE, Gouaux E (2011). Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474: 54–60.
72. Hilf RJ, Dutzler R (2008). X-ray structure of a prokaryotic ligand-gated ion channel. Nature 452: 375–379.
73. Hilf RJ, Dutzler R (2009). Structure of a potentially open state of a proton-activated pentameric ligand gated ion channel. Nature 457: 115–118.
74. Horenstein NA, Papke RL, Kulkarni AR, Chaturbhuj GU, Stokes C, Manther K et al. (2016). Critical molecular determinants of α7 nicotinic acetylcholine receptor activation. J Biol Chem 291: 5049–5067.
75. Horn R, Lange K (1983). Estimating kinetic constants from single channel data. Biophys J 43: 207–223.
76. Hu M, Gopalakrishnan M, Li J (2009). Positive allosteric modulation of alpha7 neuronal nicotinic acetylcholine receptors: lack of cytotoxicity in PC12 cells and rat primary cortical neurons. Br J Pharmacol 158: 1857–1864.
77. Hurst RS, Hajós M, Raggenbass M, Wall TM, Higdon NR, Lawson JA et al. (2005). A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci 25: 4396–4405.
78. Hurst R, Rollema H, Bertrand D (2013). Nicotinic acetylcholine receptors: from basic science to therapeutics. Pharmacol Ther 137: 22–54.
79. Husain SS, Nirthanan S, Ruesch D, Solt K, Cheng Q, Li GD et al. (2006). Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels. J Med Chem 49: 4818–4825.
80. Imoto K, Busch C, Sakmann B, Mishina M, Konno T, Nakai J et al. (1988). Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance. Nature 335: 645–648.
81. Indurthi DC, Lewis TM, Ahring PK, Balle T, Chebib M, Absalom NL (2016). Ligand binding at the α4-α4 agonist-binding site of the α4β2 nAChR triggers receptor activation through a pre-activated conformational state. PLoS One 11: e0161154. https://doi.org/10.1371/journal.pone.0161154. eCollection 2016.
82. Jackson MB (1986). Kinetics of unliganded acetylcholine receptor gating. Biophys J 49: 663–672.
83. Jackson MB (1988). Dependence of acetylcholine receptor channel kinetics on agonist concentration in cultured muscle fibres. J Physiol 397: 555–583.
84. Jackson MB (2010). Open channel block and beyond. J Physiol 588: 553–554.
85. Jayakar SS, Dailey WP, Eckenhoff RG, Cohen JB (2013). Identification of propofol binding sites in a nicotinic acetylcholine receptor with a photoreactive propofol analog. J Biol Chem 288: 6178–6189.
86. Jin X, Steinbach JH (2011). A portable site: a binding element for 17β-estradiol can be placed on any subunit of a nicotinic α4β2 receptor. J Neurosci 31: 5045–5054.
87. Jindrichova M, Lansdell SJ, Millar NS (2012). Changes in temperature have opposing effects on current amplitude in alpha7 and alpha4beta2 nicotinic acetylcholine receptors. PLoS One 7: e32073.
88. 3 receptors. Nature 424: 321–324.
89. Krause RM, Buisson B, Bertrand S, Corringer PJ, Galzi JL, Changeux JP et al. (1998). Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor. Mol Pharmacol 53: 283–294.
90. Lape RD, Colquhoun D, Sivilotti LG (2008). On the nature of partial agonism in the nicotinic receptor superfamily. Nature 454: 722–727.
91. Lee WY, Sine SM (2005). Principal pathway coupling agonist binding to channel gating in nicotinic receptors. Nature 438: 243–247.
92. Leonard RJ, Charnet P, Labarca C, Vogelaar NJ, Czyzyk L, Gouin A et al. (1991). Reverse pharmacology of the nicotinic acetylcholine receptor. mapping the local anesthetic binding site. Ann N Y Acad Sci 625: 588–599.
93. Lindstrom J, Merlie J, Yogeeswaran G (1979). Biochemical properties of acetylcholine receptor subunits from Torpedo californica. Biochem 18: 4465–4470.
94. Ludwig J, Höffle-Maas A, Samochocki M, Luttmann E, Albuquerque EX, Fels G et al. (2010). Localization by site-directed mutagenesis of a galantamine binding site on α7 nicotinic acetylcholine receptor extracellular domain. J Recept Signal Transduct Res 30: 469–483.
95. Lynagh T, Lynch JW (2012). Ivermectin binding sites in human and invertebrate Cys-loop receptors. Trends Pharmacol Sci 33: 432–441.
96. Marshall CG, Ogden D, Colquhoun D (1991). Activation of ion channels in the frog endplate by several analogs of acetylcholine. J Physiol 433: 73–93.
97. Mazzaferro S, Bermudez I, Sine SM (2017). α4β2 Nicotinic Acetylcholine Receptors: relationships between subunit stoichiometry and function at the single channel level. J Biol Chem 292: 2729–2740.
98. Methfessel C, Witzemann V, Takahashi T, Mishina M, Numa S, Sakmann B (1986). Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels. Pflugers Arch 407: 577–588.
99. Meunier JC, Sealock R, Olsen R, Changeux JP (1974). Purification and properties of the cholinergic receptor from Electrophorus electricus electric tissue. Eur J Biochem 45: 371–394.
100. Miller PS, Aricescu AR (2014). Crystal structure of a human GABAA receptor. Nature 512: 270–275.
101. Milone M, Engel AG (1996). Block of the endplate acetylcholine receptor channel by the sympathomimetic agents ephedrine, pseudoephedrine, and albuterol. Brain Res : 346–352.
102. Mishina M, Takai T, Imoto K, Noda M, Takahashi T, Numa S et al. (1986). Molecular distinction between fetal and adult forms of the acetylcholine receptor. Nature 321: 406–411.
103. Mitra AK, McCarthy MP, Stroud RM (1989). Three-dimensional structure of the nicotinic acetylcholine receptor and location of the major associated 43-kD cytoskeletal protein, determined at 22 Å by low dose electron microscopy and x-ray diffraction to 12.5 Å. J Cell Biol 109: 755–774.
104. Monod J, Wyman J, Changeux JP (1965). On the nature of allosteric transitions: a plausible model. J Mol Biol 12: 88–118.
105. Morales-Perez CL, Noviello CM, Hibbs RE (2016). X-ray structure of the human α4β2 nicotinic receptor. Nature 538: 411–415.
106. Moroni M, Zwart R, Sher E, Cassels BK, Bermudez I (2006). alpha4beta2 nicotinic receptors with high and low acetylcholine sensitivity: pharmacology, stoichiometry, and sensitivity to long-term exposure to nicotine. Mol Pharmacol 70: 755–768.
107. Mukhtasimova N, daCosta CBJ, Sine SM (2016). Improved resolution of single channel dwell times reveals mechanisms of binding, priming and gating in muscle AChR. J Gen Physiol 148: 43–63.
108. Mukhtasimova N, Lee WY, Wang HL, Sine SM (2009). Detection and trapping of intermediate states priming nicotinic receptor channel opening. Nature 459: 451–454.
109. Nagata K, Aistrup GL, Huang CS, Marszalec W, Song JH, Yeh JZ et al. (1996). Potent modulation of neuronal nicotinic acetylcholine receptor- channel by ethanol. Neurosci Lett 217: 189–193.
110. Neely A, Lingle CJ (1986). Trapping of an open-channel blocker at the frog neuromuscular acetylcholine channel. Biophys J 50: 981–986.
111. Neher E, Steinbach JH (1978). Local anaesthetics transiently block currents through single acetylcholine-receptor channels. J Physiol 277: 153–176.
112. Nelson ME, Kuryatov A, Choi CH, Zhou Y, Lindstrom J (2003). Alternate stoichiometries of alpha4beta2 nicotinic acetylcholine receptors. Mol Pharmacol 63: 332–341.
113. Nirthanan S, Garcia G 3rd, Chiara DC, Husain SS, Cohen JB (2008). Identification of binding sites in the nicotinic acetylcholine receptor for TDBzl-etomidate, a photoreactive positive allosteric effector. J Biol Chem 283: 22051–22062.
114. Noda M, Takahashi H, Tanabe T, Toyosato M, Kikyotani S, Furutani Y et al. (1983). Structural homology of Torpedo californica acetylcholine receptor subunits. Nature 302: 528–532.
115. Nury H, Van Renterghem C, Weng Y, Tran A, Baaden M, Dufresne V et al. (2011). X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel. Nature 469: 428–431.
116. Nys M, Wijckmans E, Farinha A, Yoluk Ö, Andersson M, Brams M et al. (2016). Allosteric binding site in a Cys-loop receptor ligand-binding domain unveiled in the crystal structure of ELIC in complex with chlorpromazine. Proc Natl Acad Sci U S A 113: E6696–E6703.
117. Ohno K, Wang HL, Milone M, Bren N, Brengman JM, Nakano S et al. (1996). Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. Neuron 17: 157–170.
118. Pałczyńska MM, Jindrichova M, Gibb AJ, Millar NS (2012). Activation of α7 nicotinic receptors by orthosteric and allosteric agonists: influence on single-channel kinetics and conductance. Mol Pharmacol 82: 910–917.
119. Paradiso K, Zhang J, Steinbach JH (2001). The C terminus of the human nicotinic alpha4beta2 receptor forms a binding site required for potentiation by an estrogenic steroid. J Neurosci 21: 6561–6568.
120. Qin F, Auerbach A, Sachs F (1996). Estimating single-channel kinetic parameters from idealized patch-clamp data containing missed events. Biophys J 70: 264–280.
121. Raftery MA, Hunkapiller MW, Strader CD, Hood LE (1980). Acetylcholine receptor: complex of homologous subunits. Science 208: 1454–1456.
122. Rayes D, De Rosa MJ, Spitzmaul G, Bouzat C (2001). The anthelmintic pyrantel acts as a low efficacious agonist and an open-channel blocker of mammalian acetylcholine receptors. Neuropharmacology 41: 238–245.
123. Rayes D, Flamini M, Hernando G, Bouzat C (2007). Activation of single nicotinic receptor channels from Caenorhabditis elegans muscle. Mol Pharmacol 71: 1407–1415.
124. Rayes D, De Rosa MJ, Sine SM, Bouzat C (2009). Number and Locations of Agonist Binding Sites Required to Activate Homomeric Cys-loop Receptors. J Neurosci 29: 6022–6032.
125. Reynolds JA, Karlin A (1978). Molecular weight in detergent solution of acetylcholine receptor from Torpedo californica. Biochem 17: 2035–2038.
126. Roux B, Sauve R (1985). A general solution to the time interval omission problem applied to single channel analysis. Biophys J 48: 149–158.
127. Sakmann B, Patlak J, Neher E (1980). Single acetylcholine-activated channels show burst-kinetics in presence of desensitizing concentrations of agonist. Nature 286: 71–73.
128. Sauguet L, Howard RJ, Malherbe L, Lee US, Corringer PJ, Harris RA et al. (2013). Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel. Nat Commun 4: 1697. https://doi.org/10.1038/ncomms2682.
129. Sauguet L, Shahsavar A, Poitevin F, Huon C, Menny A, Nemecz À et al. (2014). Crystal structures of a pentameric ligand-gated ion channel provide a mechanism for activation. Proc Natl Acad Sci U S A 111: 966–971.
130. Sauguet L, Shahsavar A, Delarue M (2015). Crystallographic studies of pharmacological sites in pentameric ligand-gated ion channels. Biochim Biophys Acta 1850: 511–523.
131. Sigworth FJ (1983). An example of analysis. In: Sakmann B, Neher E (eds). Single-Channel Recording, 1st edn. Plenum Press: NY.
132. Sigworth FJ (1986). The patch clamp is more useful than anyone had expected. Fed Proc 45: 2673–2677.
133. Sivilotti L, Colquhoun D (2016). In praise of single channel kinetics. J Gen Physiol 148: 79–88.
134. Sine SM, Steinbach JH (1984). Agonists block currents through acetylcholine receptor channels. Biophys J 46: 277–283.
135. Sine SM, Claudio T, Sigworth FJ (1990). Activation of Torpedo acetylcholine receptors expressed in mouse fibroblasts. Single channel current kinetics reveal distinct agonist binding affinities. J Gen Physiol 96: 395–437.
136. Sine SM, Huang S, Li SX, daCosta CJB, Chen L (2013). Inter-residue coupling contributes to high affinity, subtype selective binding of α-bungarotoxin to nicotinic receptors. Biochem J 454: 311–321.
137. Sine SM (2012). End-plate acetylcholine receptor: structure, mechanism, pharmacology and disease. Physiol Rev 92: 1189–1234.
138. Sitzia F, Brown JT, Randall AD, Dunlop J (2011). Voltage- and temperature-dependent allosteric modulation of alpha7 nicotinic receptors by PNU120596. Front Pharmacol 2: 81.
139. Southan C, Sharman JL, Benson HE, Faccenda E, Pawson AJ, Alexander SPH et al. (2016). The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Nucl Acids Res 44 (Database Issue): D1054–D1068.
140. Spitzmaul GF, Esandi MC, Bouzat C (1999). Amphetamine acts as a channel blocker of the acetylcholine receptor. Neuroreport 10: 2175–2181.
141. Spitzmaul G, Dilger JP, Bouzat C (2001). The noncompetitive inhibitor quinacrine modifies the desensitization kinetics of muscle acetylcholine receptors. Mol Pharmacol 60: 235–243.
142. Spitzmaul G, Gumilar F, Dilger JP, Bouzat C (2009). The local anaesthetics proadifen and adiphenine inhibit nicotinic receptors by different molecular mechanisms. Br J Pharmacol 157: 804–817.
143. Spurny R, Debaveye S, Farinha A, Veys K, Vos AM, Gossas T et al. (2015). Molecular blueprint of allosteric binding sites in a homologue of the agonist-binding domain of the α7 nicotinic acetylcholine receptor. Proc Natl Acad Sci 112: E2543–E2552.
144. Szabo AK, Pesti K, Mike A, Vizi ES (2014). Mode of action of the positive modulator PNU-120596 on α7 nicotinic acetylcholine receptors. Neuropharmacology 81: 42–54.
145. Tamamizu S, Guzman GR, Santiago J, Rojas LV, McNamee MG, Lasalde Dominicci JA (2000). Functional effects of periodic tryptophan substitutions in the alpha M4 transmembrane domain of the Torpedo californica nicotinic acetylcholine receptor. Biochem 39: 4666–4673.
146. Thinschmidt JS, López-Hernández GY, Ren K, King MA, Meyer EM, Papke RL (2008). Modulation of spontaneous hippocampal synaptic events with 5-hydroxyindole, 4OH-GTS-21, and rAAV-mediated alpha7 nicotinic receptor gene transfer. Brain Res 1203: 51–60.
147. Toyoshima C, Unwin N (1988). Ion channel of acetylcholine receptor reconstructed from images of postsynaptic membranes. Nature 336: 247–250.
148. Uteshev VV (2014). The therapeutic promise of positive allosteric modulation of nicotinic receptors. Eur J Pharmacol 727: 181–185.
149. Uteshev V (2016). Are positive allosteric modulators of α7 nAChRs clinically safe? J Neurochem 136: 217–219.
150. Unwin N (1993). Nicotinic acetylcholine receptor at 9 Å resolution. J Mol Biol 229: 1101–1124.
151. Unwin N (2005). Refined structure of the nicotinic receptor at 4 Å resolution. J Mol Biol 346: 967–989.
152. Vallés AS, Garbus I, Barrantes FJ (2007). Lamotrigine is an open-channel blocker of the nicotinic acetylcholine receptor. Neuroreport 18: 45–50.
153. Williams DK, Wang J, Papke RL (2011). Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations. Biochem Pharmacol 82: 915–930.
154. Williams DK, Peng C, Kimbrell MR, Papke RL (2012). Intrinsically low open probability of α7 nicotinic acetylcholine receptors can be overcome by positive allosteric modulation and serum factors leading to the generation of excitotoxic currents at physiological temperatures. Mol Pharmacol 82: 746–759.
155. Yan H, Pan N, Xue F, Zheng Y, Li C, Chang Y et al. (2015). The coupling interface and pore domain codetermine the single-channel activity of the α7 nicotinic receptor. Neuropharmacology 95: 448–458.
156. Young GT, Zwart R, Walker AS, Sher E, Millar NS (2008). Potentiation of α7 nicotinic acetylcholine receptors via an allosteric transmembrane site. Proc Natl Acad Sci U S A 105: 14686–14691.
157. Zanetti SR, Ziblat A, Torres NI, Zwirner NW, Bouzat C (2016). Expression and functional role of α7 nicotinic receptor in human cytokine-stimulated natural killer (NK) cells. J Biol Chem 291: 16541–16552.
158. Zhang Y, Chen J, Auerbach A (1995). Activation of recombinant mouse acetylcholine receptors by acetylcholine, carbamylcholine and tetramethylammonium. J Physiol 486: 189–206.
159. Zhou Y, Nelson ME, Kuryatov A, Choi C, Cooper J, Lindstrom J (2003). Human alpha4beta2 acetylcholine receptors formed from linked subunits. J Neurosci 23: 9004–9015.
160. Zuo Y, Aistrup GL, Marszalec W, Gillespie A, Chavez-Noriega LE, Yeh JZ et al. (2001). Dual action of n-alcohols on neuronal nicotinic acetylcholine receptors. Mol Pharmacol 60: 700–711.