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Developmental regulation of multiple nicotinic AChR channel subtypes in embryonic chick habenula neurons: contributions of both theα2 andα4 subunit genes

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  • Molecular and Cellular Physiology
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Abstract

Habenula neurons from both early and late stage embryonic chickens express multiple subtypes of nicotinic acetylcholine receptor channels (nAChRs). The channel subtypes expressed by habenula neurons are similar in functional properties, but apparently distinct in subunit composition, from their peripheral counterparts in autonomic ganglia. Early in development, nicotine activates four classes of neuronal bungarotoxin (nBGT)-sensitive channels (approx. conductance=15, 30, 50, 60pS) that are intermingled on the surface of habenula neuronal somata. In neurons removed from older animals, nAChR channel activity has increased 4- to 40-fold and channel subtypes have become spatially segregated from one another. Analysis of the profile of nAChR subunit gene expression by polymerase chain reaction indicates that several of theα-type subunit genes, includingα2,3,4,5,7, andα8, as well as bothβ2 andβ4, are expressed. Treatment of the neurons with subunit specific antisense oligonucleotides reveals that theα2 andα4 (but notα3) subunits contribute to the functional profile of native nAChRs expressed by habenula neurons. Consideration of the functional properties and apparent subunit composition of autonomic ganglion nAChRs in the chick suggests that habenula neurons may utilize a very distinct set of subunit combinations to produce an array of nAChR channel subtypes similar in both conductance and pharmacological profile to those expressed by sympathetic neurons.

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References

  1. Aizenman E, Loring RH, Lipton SA (1990) Blockade of nicotinic responses in rat retinal ganglion cells by neuronal bungarotoxin. Brain Res 517:209–214

    Article  PubMed  CAS  Google Scholar 

  2. Alkondon M, Albuquerque EX (1993) Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. I. Pharmacological and functional evidence for distinct structural subtypes. J Pharmacol Exp Ther 265:1455–1473

    PubMed  CAS  Google Scholar 

  3. Boyd RT, Jacob MH, Couturier S, Ballivet M, Berg DK (1988) Expression and regulation of neuronal acetylcholine receptor mRNA in chick ciliary ganglia. Neuron 1:495–502

    Article  PubMed  CAS  Google Scholar 

  4. Boyd RT, Jacob MH, McEachern AE, Caron S, Berg DK (1991) Nicotinic acetylcholine receptor mRNA in dorsal root ganglion neurons. J Neurobiol 22:1–14

    Article  PubMed  CAS  Google Scholar 

  5. Brehm P, Henderson L (1988) Regulation of acetylcholine receptor channel function during development of skeletal muscle. Dev Biol 129:1–11

    Article  PubMed  CAS  Google Scholar 

  6. Colquhoun L, Dineley K, Patrick J (1933) A hetero-beta neuronal nicotinic acetylcholine receptor expressed in Xenopus oocytes. Soc Neurosci Abstr 19:1533

    Google Scholar 

  7. Conroy WG, Vernallis AB, Berg DK (1992) Theα5 gene product assembles with multiple acetylcholine receptor subunits to form distinctive receptor subtypes in brain. Neuron 9:679–691

    Article  PubMed  CAS  Google Scholar 

  8. Corriveau RA, Berg DK (1993) Coexpression of multiple acetylcholine receptor genes in neurons: quantification of transcripts during development. J Neurosci 13:2662–2671

    PubMed  CAS  Google Scholar 

  9. Reference deleted

  10. Devay P, Qu X, Role L (1994) Regulation of nAChR subunit gene expression relative to the development of pre- and postsynaptic projections of embryonic chick sympathetic neurons. Dev Biol 162:56–70

    Article  PubMed  CAS  Google Scholar 

  11. Gardette R, Listerud M, Brussaard AB, Role LW (1991) Developmental changes in transmitter sensitivity and synaptic transmission in embryonic chicken sympathetic neurons innervated in vitro. Dev Biol 147:83–95

    Article  PubMed  CAS  Google Scholar 

  12. Halvorsen SW, Berg DW (1990) Subunit composition of nicotinic acetylcholine receptors from chick ciliary ganglia. J Neurosci 10:1711–1718

    PubMed  CAS  Google Scholar 

  13. 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. Pflügers Arch 391:85–100

    Article  PubMed  CAS  Google Scholar 

  14. Heinemann S, Boulter J, Deneris E, Connolly J, Duvousin R, Papke R, Patrick J (1990) The brain nicotinic acetylcholine receptor gene family. Prog Brain Res 86:195–203

    Article  PubMed  CAS  Google Scholar 

  15. Henderson LP, Brehm P (1989) The single-channel basis for the slow kinetics of synaptic currents in vertebrate slow muscle fibers. Neuron 2:1399–1405

    Article  PubMed  CAS  Google Scholar 

  16. Houser CR, Crawford GD, Barber RP, Salvaterra PM, Vaughn JE (1983) Organization and morphological characterization of cholinergic neurons: an immunocytochemical study with a monoclonal antibody to choline acetyltransferase. Brain Res 266:97–119

    Article  PubMed  CAS  Google Scholar 

  17. Huettner JE, Baughman RW (1986) Primary culture of identified neurons from the visual cortex of postnatal rats. J Neurosci 6:3044–3060

    PubMed  CAS  Google Scholar 

  18. Ifune CK, Steinbach JH (1991) Voltage-dependent block by magnesium of neuronal nicotinic acetylcholine receptor channels in rat pheochromocytoma cells. J Physiol (Lond) 443:683–701

    CAS  Google Scholar 

  19. Jaramillo F, Schuetze SM (1988) Kinetic differences between embryonic- and adult-type acetylcholine receptors in rat myotubes. J Physiol (Lond) 396:267–296

    CAS  Google Scholar 

  20. Johnson CD, Epstein ML (1986) Monoclonal antibodies and polyvalent antiserum to chicken choline acetyltransferase. J Neurochem 46:968–976

    Article  PubMed  CAS  Google Scholar 

  21. Kidokoro Y (1988) Developmental changes in acetylcholine receptor channel properties of vertebrate skeletal muscle. Ion Channels 1:163–182

    PubMed  CAS  Google Scholar 

  22. Kidokoro Y, Bohrbough J (1990) Acetylcholine receptors channels in xenopus myocyte culture; brief opening, brief closures and slow desensitization. J Physiol (Lond) 425:227–244

    CAS  Google Scholar 

  23. Lena C, Changeux JP, Mulle C (1993) Evidence for preterminal nicotinic receptors on GABAergic axons in the rat interpeduncular nucleus. J Neurosci 13:2680–2688

    PubMed  CAS  Google Scholar 

  24. Levey AI, Hallanger AE, Wainer BH (1987) Choline acetyltransferase in the rat thalamus. J Comp Neurol 257:317–332

    Article  PubMed  CAS  Google Scholar 

  25. Lipscombe D, Rang HP (1988) Nicotinic receptors of frog ganglia resemble pharmacologically those of skeletal muscle. J Neurosci 8:3258–3265

    PubMed  CAS  Google Scholar 

  26. Listerud M, Brussaard AB, Devay P, Colman DR, Role LW (1991) Functional contribution of individual neuronal nAChR subunits revealed by antisense oligonucleotides. Science 254:1518–1521

    Article  PubMed  CAS  Google Scholar 

  27. Loring RH, Aizenman E, Lipton SA, Zigmond RE (1989) Characterization of nicotinic receptors in chick retina using a snake venom neurotoxin that blocks neuronal nicotinic receptors function. J Neurosci 9:2423–2431

    PubMed  CAS  Google Scholar 

  28. Lu B, Fu WM, Greengard P, Poo MM (1993) Calcitonin generelated peptide potentiates synaptic responses at developing neuromuscular junction. Nature 363:76–79

    Article  PubMed  CAS  Google Scholar 

  29. Luetje CW, Patrick J, Seguela P (1990) Nicotine receptors in the mammalian brain. FASEB J 4:2753–2760

    PubMed  CAS  Google Scholar 

  30. Luetje CW, Wada K, Roger S, Abramson SN, Tsuji K, Heinemann S, Patrick J (1990) Neurotoxin distinguish between different neuronal nicotinic acetylcholine receptors subunit combinations. J Neurochem 55:632–640

    Article  PubMed  CAS  Google Scholar 

  31. Margiotta JF, Gurantz D (1989) Changes in the number, function, and regulation of nicotinic acetylcholine receptors during neuronal development. Dev Biol 135:326–339

    Article  PubMed  CAS  Google Scholar 

  32. Mathie A, Colquhoun D, Cull-Candy SG (1990) Rectification of current activated by nicotinic acetylcholine receptors in rats sympathetic ganglion neurones. J Physiol (Lond) 427:625–655

    CAS  Google Scholar 

  33. Mathie A, Cull-Candy SG, Colquhoun D (1991) Conductance and kinetic properties of single nicotinic acetylcholine receptor channels in rat sympathetic neurons. J Physiol (Lond) 439:717–750

    CAS  Google Scholar 

  34. Matter JM, Sadzinski LM, Ballivet M (1990) Expression of neuronal nicotinic acetylcholine receptors genes in the developing chick visual system. EMBO J 9:1021–1026

    PubMed  CAS  Google Scholar 

  35. Middleton P, Rubin LL, Schuetze SM (1988) Modulation of acetylcholine receptor desensitization in rat myotubes. J Neurosci 8:3405–3412

    PubMed  CAS  Google Scholar 

  36. Morris BJ, Hick AA, Wisden W, Darlison MG, Hunt SP, Barnard EA (1990) Distinct regional expression of nicotinic acetylcholine receptors genes in chick brain. Mol Brain Res 7:305–315

    Article  PubMed  CAS  Google Scholar 

  37. Moss BL, Role LW (1993) Enhanced ACh sensitivity is accompanied by changes in ACh receptor channel properties and segregation of ACh receptor subtypes on sympathetic neurons during innervation in vivo. J Neurosci 13:13–28

    PubMed  CAS  Google Scholar 

  38. Moss BL, Schuetze SM, Role LW (1989) Functional properties and developmental regulation of nicotinic acetylcholine receptors on embryonic chicken sympathetic neurons. Neuron 3:597–607

    Article  PubMed  CAS  Google Scholar 

  39. Mulle C, Changeux JP (1990) A novel type of nicotinic receptors in the rat central nervous system characterized by patchtechniques. J Neurosci 10:169–175

    PubMed  CAS  Google Scholar 

  40. Mulle C, Vidal C, Benoit P, Changeux JP (1991) Existence of different subtypes of nicotinic acetylcholine receptors in the rat habenulo-interpeduncular system. J Neurosci 11:2588–2592

    PubMed  CAS  Google Scholar 

  41. Nakayama HN, Shirasi M, Nakashima T, Kurogochi Y, Lindstrom JM (1990) Affinity purification of nicotinic acetylcholine receptor from rat brain. Mol Brain Res 7:221–226

    Article  PubMed  CAS  Google Scholar 

  42. Reference deleted

  43. Owens JL, Kullberg R (1989) Three conductance classes of nicotinic acetylcholin receptors are expressed in developing amphibian skeletal muscle. J Neurosci 9:2573–2580

    Google Scholar 

  44. Papke RL, Heinemann SF (1991) The role of theβ4-subunit in determining the kinetic properties of rat neuronal nicotinic acetylcholineα3 receptors. J Physiol (Lond) 440:95–112

    CAS  Google Scholar 

  45. Papke RL, Boulter J, Patrick J, Heinemann S (1989) Single-channel current of rat neuronal nicotinic acetylcholine receptors expressed in xenopus oocytes. Neuron 3:589–596

    Article  PubMed  CAS  Google Scholar 

  46. Ramirez-Latorre JA, Qu X, Karlin A, Role L (1993) Participation ofα5 in neuronal nicotinic AChR channels. Soc Neurosci Abstr 19:1533(630.8)

    Google Scholar 

  47. Rohrbough J, Kidokoro Y (1990) Changes in kinetic acetylcholine receptors channels after initial expression in xenopus myocyte culture. J Physiol (Lond) 425:245–269

    CAS  Google Scholar 

  48. Role LW (1984) Substance P modulation of acetylcholine-induced currents in embryonic chicken sympathetic and ciliary ganglion neurons in vitro. Proc Natl Acad Sci USA 81:2924–2928

    Article  PubMed  CAS  Google Scholar 

  49. Role LW (1992) Diversity in primary structure and function of neuronal nicotinic acetylcholine receptor channels. Curr Opin Neurobiol 2:254–262

    Article  PubMed  CAS  Google Scholar 

  50. Sargent PB (1993) The diversity of neuronal nicotinic acetylcholine receptors. Annu Rev Neurosci 16:403–443 51. Reference deleted

    Article  PubMed  CAS  Google Scholar 

  51. Silman I, Karlin A (1969) Acetylcholine receptor covalent attachment of depolarizing groups at the active site. Science 164:1420–1421

    Article  PubMed  CAS  Google Scholar 

  52. Snedecor GW, Cochran WG (1967) In: Statistical methods, 6th edn, Iowa University Press, p 329

  53. Sorenson EM, Chiappinelli VA (1990) Intracellular recording in avian brain of a nicotinic response that is intensive to k-bungarotoxin. Neuron 5:307–315

    Article  PubMed  CAS  Google Scholar 

  54. Sorenson EM, Parkinson D, Dahl JL, Chiappinelli VA (1989) Immunohistochemical localization of choline acetyltransferase in the chicken mesencephalon. J Comp Neurol 281:641–657

    Article  PubMed  CAS  Google Scholar 

  55. Swanson LW, Lindstrom J, Tzartos S, Schmued LC, O'Leary DDM, Cowan WM (1983) Immunohistochemical localization of monoclonal antibodies to the nicotinic acetylcholine receptors in the chick midbrain. Proc Natl Acad Sci USA 80:4532–4536

    Article  PubMed  CAS  Google Scholar 

  56. Vernino S, Amador M, Luetje CW, Patrick J, Dani JA (1992) Calcium modulation and high calcium permeability of neuronal nicotinic acetylcholine receptors. Neuron 8:127–134

    Article  PubMed  CAS  Google Scholar 

  57. Wada E, McKinnon D, Heinemann S, Patrick J, Swanson LW (1990) The distribution of mRNA encoded by a new member of the neuronal nicotinic acetylcholine receptors gene family (α5) in the rat central nervous system. Brain Res 526:45–53

    Article  PubMed  CAS  Google Scholar 

  58. Wada E, Wada K, Boulter J, Deneris E, Heinemann S, Patrick J, Swanson LW (1990) Distribution ofα2,α3,α4, andβ2 neuronal nicotinic receptors subunit mRNAs in the central nervous system: a hybridization histochemical study in the rat. J Comp Neurol 284:314–335

    Article  Google Scholar 

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Author notes

  1. Arjen B. Brussaard

    Present address: Neurophysiology, Department of Biology, Free University Amsterdam, de Boelelaan 1087, 1081, HV Amsterdam, The Netherlands

  2. Xia Yang & Joseph P. Doyle

    Present address: Department of Molecular Biology, Mt Sinai School of Medicine, 10029, New York, NY, USA

  3. Sigismund Huck

    Present address: Dept. of Neuropharmacology, University of Vienna, Waehringerstr. 13A, 1090, Vienna, Austria

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Center for Neurobiology and Behavior, Columbia University P&S, Psychiatric Institute Research Annex, 22 W 168th St, 10032, New York, NY, USA

    Arjen B. Brussaard, Xia Yang, Joseph P. Doyle, Sigismund Huck & Lorna W. Role

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Brussaard, A.B., Yang, X., Doyle, J.P. et al. Developmental regulation of multiple nicotinic AChR channel subtypes in embryonic chick habenula neurons: contributions of both theα2 andα4 subunit genes. Pflugers Arch. 429, 27–43 (1994). https://doi.org/10.1007/BF02584027

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  • DOI: https://doi.org/10.1007/BF02584027

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