Skip to main content
Log in

Elevation of intracellular calcium levels in neurons by nicotinic acetylcholine receptors

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The recognition that intracellular free calcium serves as a ubiquitous intracellular signal has motivated efforts to elucidate mechanisms by which cells regulate calcium influx. One route of entry that may offer both spatial and temporal fine resolution for altering calcium levels is that provided by cation-permeable, ligand-gated ion channels. Biophysical measurements as well as calcium imaging techniques demonstrate that neuronal nicotinic acetylcholine receptors as a class have a high relative permeability to calcium; some subtypes equal or exceed all other known receptors in this respect. Activation of nicotinic receptors on neurons can produce substantial increases in intracellular calcium levels by direct passage of calcium through the receptor channel. When multiple classes of nicotinic receptors are expressed by the same neuron, each appears capable of increasing calcium in the cell but may differ with respect to location, temporal response, agonist sensitivity, or regulation in achieving it. As a result, nicotinic receptors must be considered strong candidates for signaling molecules through which neurons regulate a diverse array of cellular events.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bading H., Ginty D. D., and Greenberg M. E. (1993) Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways.Science 260, 181–186.

    Article  PubMed  CAS  Google Scholar 

  2. Walke W., Staple J., Adams L., Gnegy M., Chahine K., and Goldman D. (1994) Calcium-dependent regulation of rat and chick muscle nicotinic acetylcholine receptor (nAChR) gene expression.J. Biol. Chem. 269, 19,447–19,456.

    CAS  Google Scholar 

  3. Ghosh A. and Greenberg M. E. (1995) Calcium signaling in neurons: molecular mechanisms and cellular consequences.Science 268, 239–247.

    Article  PubMed  CAS  Google Scholar 

  4. Bliss T. V. and Collingridge G. L. (1993) A synaptic model of memory: long-term potentiation in the hippocampus.Nature 361, 31–39.

    Article  PubMed  CAS  Google Scholar 

  5. Mattson M. P. (1992) Calcium as sculptor and destroyer of neural circuitry.Exp. Gerontol. 27, 29–49.

    Article  PubMed  CAS  Google Scholar 

  6. Choi D. W. (1992) Excitotoxic cell death.J. Neurobiol. 23, 1261–1276.

    Article  PubMed  CAS  Google Scholar 

  7. Gunter T. E. and Pfeiffer D. R. (1990) Mechanisms by which mitochondria transport calcium.Am. J. Physiol. 258, C755-C786.

    PubMed  CAS  Google Scholar 

  8. Thayer S. A. and Miller R. J. (1990) Regulation of the intracellular free calcium concentration in single rat dorsal root ganglion neurons in vitro.J. Physiol. (Lond.) 425, 85–115.

    CAS  Google Scholar 

  9. Fabiato A. (1983) Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum.Am. J. Physiol. 245, C1-C14.

    PubMed  CAS  Google Scholar 

  10. Ruegg J. C. (1992) Calcium in muscle contraction: cellular and molecular physiology, inCalcium in Muscle Contraction, 2nd ed. (Ruegg J. C., ed.), Springer Verlag, Berlin.

    Google Scholar 

  11. Roberts W. M. (1993) Spatial calcium buffering in saccular hair cells.Nature 363, 74–76.

    Article  PubMed  CAS  Google Scholar 

  12. Roberts W. M. (1994) Localization of calcium signals by a mobile calcium buffer in frog saccular hair cells.J. Neurosci. 14, 3246–3264.

    PubMed  CAS  Google Scholar 

  13. Augustine G. J., Charlton M. P., and Smith S. J. (1985) Calcium entry and transmitter release at voltage-clamped nerve terminals of squid.J. Physiol. (Lond.) 369, 163–181.

    Google Scholar 

  14. Fogelson A. L. and Zucker R. S. (1985) Presynaptic calcium diffusion from various arrays of single channels. Implication for transmitter release and synaptic facilitation.Biophys. J. 48, 1003–1007.

    PubMed  CAS  Google Scholar 

  15. Simon S. M. and Llinas R. R. (1985) Compartmentalization of the submembrane calcium activity during calcium influx and its significance in transmitter release.Biophys. J. 48, 485–498.

    Article  PubMed  CAS  Google Scholar 

  16. Augustine G. J. and Neher E. (1992) Neuronal Ca2+ signaling takes the local route.Curr. Opin. Neurobiol. 2, 302–307.

    Article  PubMed  CAS  Google Scholar 

  17. Huang C.-F., Flucher B. E., Schmidt M. M., Stroud S. K., and Schmidt J. (1994) Depolarization-transcription signals in skeletal muscle use calcium flux through L channels, but bypass the sarcoplasmic reticulum.Neuron 13, 167–177.

    Article  PubMed  CAS  Google Scholar 

  18. Lewis C. A. (1979) Ion-concentration dependence of the reversal potential and the single channel conductance of ion channels at the frog neuromuscular junction.J. Physiol. (Lond.) 286, 417–445.

    CAS  Google Scholar 

  19. Adams D. J., Dwyer T. M., and Hille B. (1980) The permeability of endplate channels to monovalent and divalent metal cations.J. Gen. Physiol. 75, 493–510.

    Article  PubMed  CAS  Google Scholar 

  20. Mayer M. L. and Westbrook G. L. (1987) Permeation and block ofN-methyl-d-aspartic acid receptor channels by divalent cations in mouse cultured central neurones.J. Physiol. 394, 501–527.

    PubMed  CAS  Google Scholar 

  21. Ascher P. and Nowak L. (1988) The role of divalent cations in theN-methyl-d-aspartate responses of mouse central neurones in culture.J. Physiol. 399, 247–266.

    PubMed  CAS  Google Scholar 

  22. Jahr C. E. and Stevens C. F. (1993) Calcium permeability of theN-methyl-d-aspartate receptor channel in hippocampal neurons in culture.Development 90, 11,573–11,577.

    CAS  Google Scholar 

  23. Mayer M. L. and Miller R. J. (1991) Excitatory amino acid receptors, second messengers and regulation of intracellular Ca2+ in mammalian neurons.TINS 11, 254–260.

    Google Scholar 

  24. Zorumski C. F. and Thio L. L. (1992) Properties of vertebrate glutamate receptors calcium mobilization and desensitization.Prog. Neurobiol. 39, 295–336.

    Article  PubMed  CAS  Google Scholar 

  25. Scheetz A. J. and Constantine-Paton M. (1994) Modulation of NMDA receptor function implications for vertebrate neural development.FASEB J. 8, 745–751.

    PubMed  CAS  Google Scholar 

  26. Frandsen A. and Schoesboe A. (1993) Excitatory amino acid-mediated cytotoxicity and calcium homeostasis in cultured neurons.J. Neurochem. 60, 1202–1211.

    Article  PubMed  CAS  Google Scholar 

  27. Mulle C., Choquet D., Korn H., and Changeux J.-P. (1992) Calcium influx through nicotinic receptor in rat central neurons: its relevance to cellular regulation.Neuron 8, 135–143.

    Article  PubMed  CAS  Google Scholar 

  28. Vernino S., Amador M., Luetje C. W., Patrick J., and Dani J. A. (1992) Calcium modulation and high calcium permeability of neuronal nicotinic acetylcholine receptors.Neuron 8, 127–134.

    Article  PubMed  CAS  Google Scholar 

  29. Rathouz M. M. and Berg D. K. (1994) Synaptic-type acetylcholine receptors raise intracellular calcium levels in neurons by two mechanisms.J. Neurosci. 14, 6935–6945.

    PubMed  CAS  Google Scholar 

  30. Bertrand D., Galzi J. L., Devillers-Thiery A., Bertrand S., and Changeux J. P. (1993) Mutations at two distinct sites within the channel domain M2 alter calcium permeability of neuronal α7 nicotinic receptor.Proc. Natl. Acad. Sci. USA 90, 6971–6975.

    Article  PubMed  CAS  Google Scholar 

  31. Seguela P., Wadiche J., Dineley-Miller K., Dani J. A., and Patrick J. W. (1993) Molecular cloning, functional properties, and distribution of rat brain α7: a nicotinic cation channel highly permeable to calcium.J. Neurosci. 13, 596–604.

    PubMed  CAS  Google Scholar 

  32. Vijayaraghavan S., Pugh P. C., Zhang Z.-W., Rathouz M. M., and Berg D. K. (1992) Nicotinic receptors that bind α-bungarotoxin on neurons raise intracellular free Ca2+.Neuron 8, 353–362.

    Article  PubMed  CAS  Google Scholar 

  33. Dani J. A. (1993) Structure, diversity, and ionic permeability of neuronal and muscle acetylcholine receptors.EXS 66, 47–59.

    PubMed  CAS  Google Scholar 

  34. Sargent P. B. (1993) The diversity of neuronal nicotinic acetylcholine receptors.Ann. Rev. Neurosci. 10, 403–457.

    Article  Google Scholar 

  35. McGehee D. S. and Role L. W. (1995) Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons.Ann. Rev. Physiol. 57, 521–546.

    Article  CAS  Google Scholar 

  36. Fieber L. A. and Adams D. J. (1991) Acetylcholine-evoked currents in cultured neurones dissociated from rat parasympathetic cardiac ganglia.J. Physiol. 434, 215–237.

    PubMed  CAS  Google Scholar 

  37. Sands S. B. and Barish M. E. (1991) Calcium permeability of neuronal nicotinic acetylcholine receptor channels in PC12 cells.Brain Res. 560, 38–42.

    Article  PubMed  CAS  Google Scholar 

  38. Sands S. B., Costa A. C. S., and Patrick J. W. (1993) Barium permeability of neuronal nicotinic receptor α7 expressed inXenopus oocytes.Biophys. J. 65, 2614–2621.

    PubMed  CAS  Google Scholar 

  39. Dani J. A. and Eisenman G. (1987) Monovalent and divalent cation permeation in acetylcholine receptor channels.J. Gen. Physiol. 89, 959–983.

    Article  PubMed  CAS  Google Scholar 

  40. Decker E. R. and Dani J. A. (1990) Calcium permeability of the nicotinic acetylcholine receptor: the single-channel calcium influx is significant.J. Neurosci. 10, 3413–3420.

    PubMed  CAS  Google Scholar 

  41. Couturier S., Bertrand D., Matter J.-M., hernandez M.-C., Bertrand S., Miller N., Valera S., Barkas T., and Ballivet M. (1990) A neuronal nicotinic acetylcholine receptor subunit (α7) is developmentally regulated and forms a homo-oligomeric channel blocked by α-bungarotoxin.Neuron 5, 847–856.

    Article  PubMed  CAS  Google Scholar 

  42. Galzi J.-L., Devillers-Thiery A., Hussy N., Bertrand S., Changeux J.-P., and Bertrand D. (1992) Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic.Nature 359, 500–505.

    Article  PubMed  CAS  Google Scholar 

  43. Castro N. G. and Albuquerque E. X. (1995) αBungarotoxin-sensitive hippocampal nicotinic receptor channel has a high calcium permeability.Biophys. J. 68, 516–524.

    PubMed  CAS  Google Scholar 

  44. Elgoyhen A. B., Johnson D. S., Boulter J., Vetter D. E., and Heinemann S. (1994) α9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells.Cell 79, 705–715.

    Article  PubMed  CAS  Google Scholar 

  45. Hume R. I., Dingledine R., and Heinemann S. F. (1991) Identification of a site in glutamate receptor subunits that controls calcium permeability.Science 253, 1028–1031.

    Article  PubMed  CAS  Google Scholar 

  46. Burnashev N., Monyer H., Seeburg P. H., and Sakmann B. (1992) Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit.Neuron 8, 189–198.

    Article  PubMed  CAS  Google Scholar 

  47. Burnashev N., Schoepfer R., Monyer H., Ruppersberg J. P., Gunther W., Seeburg P. H., and Sakmann B. (1992) Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor.Science 257, 1415–1419.

    Article  PubMed  CAS  Google Scholar 

  48. Treinin M. and Chalfie M. (1995) A mutated acetylcholine receptor subunit causes neuronal degeneration inC. elegans.Neuron 14, 871–877.

    Article  PubMed  CAS  Google Scholar 

  49. Minta A., Kao J. P. Y., and Tsien R. Y. (1989) Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores.J. Biol. Chem. 264, 8171–8178.

    PubMed  CAS  Google Scholar 

  50. Schneggenburger R., Zhou Z., Konnerth A., and Neher E. (1993) Fractional contribution of calcium to the cation current through glutamate receptor channels.Neuron 11, 133–143.

    Article  PubMed  CAS  Google Scholar 

  51. Trouslard J., Marsh S. J., and Brown D. A. (1993) Calcium entry through nicotinic receptor channels and calcium channels in cultured rat superior cervical ganglion cells.J. Physiol. 468, 53–71.

    PubMed  CAS  Google Scholar 

  52. Zhou Z. and Neher E. (1993) Calcium permeability of nicotinic acetylcholine receptor channels in bovine adrenal chromaffin cells.Pflugers Arch. 425, 511–517.

    Article  PubMed  CAS  Google Scholar 

  53. Vernino S., Rogers M., Radcliffe K. A., and Dani J. A. (1994) Quantitative measurement of calcium flux through muscle and neuronal nicotinic acetylcholine receptors.J. Neurosci. 14, 5514–5524.

    PubMed  CAS  Google Scholar 

  54. Rathouz M. M. (1995) Regulation of intracellular free calcium by cholinergic receptors on chick CG neurons, PhD dissertation, University of California, San Diego.

    Google Scholar 

  55. Rogers M. and Dani J. A. (1995) Comparison of quantitative calcium flux through NMDA, ATP, and ACh receptor channels.Biophys. J. 68, 501–506.

    PubMed  CAS  Google Scholar 

  56. Tsien R. W. and Tsien R. Y. (1990) Calcium channels, stores and oscillations.Ann. Rev. Cell Biol. 6, 715–760.

    Article  PubMed  CAS  Google Scholar 

  57. Pilar G. and Tuttle J. B. (1982) A simple neuronal system with a range of uses: the avian ciliary ganglion, inProgress in Cholinergic Biology: Model Cholinergic Synapses (Hanin I. and Goldberg A. M., eds.), Raven, New York, pp. 213–247.

    Google Scholar 

  58. Corriveau R. A. and Berg D. K. (1993) Coexpression of multiple acetylcholine receptor genes in neurons: quantification of transcripts during development.J. Neurosci. 13, 2662–2671.

    PubMed  CAS  Google Scholar 

  59. Vernallis A. B., Conroy W. G., and Berg D. K. (1993) Neurons assemble acetylcholine receptors with as many as three kinds of subunits and can segregate subunits among receptor subtypes.Neuron 10, 451–464.

    Article  PubMed  CAS  Google Scholar 

  60. Zhang Z. W., Vijayaraghavan S., and Berg D. K. (1994) Neuronal acetylcholine receptors that bind α-bungarotoxin with high affinity function as ligand-gated ion channels.Neuron 12, 167–177.

    Article  PubMed  CAS  Google Scholar 

  61. Conroy W. G. and Berg D. K. (1995) Neurons can maintain multiple classes of nicotinic acetylcholine receptors distinguished by different subunit compositions.J. Biol. Chem. 270, 4424–4431.

    Article  PubMed  CAS  Google Scholar 

  62. Pugh P. C., Corriveau R. A., Conroy W. G., and Berg D. K. (1995) A novel subpopulation of neuronal acetylcholine receptors among those binding α-bungarotoxin.Mol. Pharmacol. 47, 717–725.

    PubMed  CAS  Google Scholar 

  63. Jacob M. H. and Berg D. K. (1983) The ultrastructural localization of α-bungarotoxin binding sites in relation to synapses on chick ciliary ganglion neurons.J. Neurosci. 3, 260–271.

    PubMed  CAS  Google Scholar 

  64. Loring R. H., Dahm R. H., and Zigmond R. E. (1985) Localization of α-bungarotoxin binding sites in the ciliary ganglion of the embryonic chick: an autoradiographic study at the light and electron microscopic level.Neuroscience 14, 645–660.

    Article  PubMed  CAS  Google Scholar 

  65. Wilson-Horch H. L. and Sargent P. B. (1995) Perisynaptic surface distribution of multiple classes of nicotinic acetylcholine receptors on neurons in the chicken ciliary ganglion.J. Neurosci. 15, 7778–7795.

    Google Scholar 

  66. Jacob M. H., Berg D. K., and Lindstrom J. M. (1984) Shared antigenic determinant between theElectrophorus acetylcholine receptor and a synaptic component on chicken ciliary ganglion neurons.Proc. Natl. Acad. Sci. USA 81, 3223–3227.

    Article  PubMed  CAS  Google Scholar 

  67. Loring R. H. and Zigmond R. E. (1987) Ultrastructural distribution of125I-toxin F binding sites on chick ciliary neurons: synaptic localization of a toxin that blocks ganglionic nicotinic receptors.J. Neurosci. 7, 2153–2162.

    PubMed  CAS  Google Scholar 

  68. Chiappinelli V. A., Cohen J. B., and Zigmond R. E. (1981) The effects of α- and β-neurotoxins from the venoms of various snakes on transmission in autonomic ganglia.Brain Res. 211, 107–126.

    Article  PubMed  CAS  Google Scholar 

  69. Sorimachi M. (1995) Pharmacology of nicotine-induced increase in cytosolic Ca2+ concentrations in chick embryo ciliary ganglion cells.Brain Res. 669, 26–34.

    Article  PubMed  CAS  Google Scholar 

  70. Sorimachi M. (1993) Caffeine- and muscarinic agonist-sensitive Ca2+ stores in chick ciliary ganglion cells.Brain Res. 627, 34–40.

    Article  PubMed  CAS  Google Scholar 

  71. Furukawa K., Abe Y., Sorimachi M., and Akaike N. (1994) Nicotinic and muscarinic acetylcholine responses in the embryo chick ciliary ganglion cells.Brain Res. 657, 185–190.

    Article  PubMed  CAS  Google Scholar 

  72. Rathouz M. M., Vijayaraghavan S., and Berg D. K. (1995) Acetylcholine differentially affects intracellular calcium via nicotinic and muscarinic receptors on the same population of neurons.J. Biol. Chem. 270, 14,366–14,375.

    CAS  Google Scholar 

  73. Cornell-Bell A. H., Finkbeiner S. M., Cooper, M. S., and Smith S. J. (1990) Glutamate induces calcium waves in cultured astrocytes: longrange glial signaling.Science 247, 470–473.

    Article  PubMed  CAS  Google Scholar 

  74. Gray D. B., Zelazny D., Manthay N., and Pilar G. (1990) Endogenous modulation of ACh release by somatostatin and the differential roles of Ca2+ channels.J. Neurosci. 10, 2687–2698.

    PubMed  CAS  Google Scholar 

  75. Tymianski M., Charlton M. P., Carlen P. L., and Tator C. H. (1993) Source specificity of early calcium neurotoxicity in cultured embryonic spinal neurons.J. Neurosci. 13, 2085–2104.

    PubMed  CAS  Google Scholar 

  76. Fuchs P. A. and Murrow B. W. (1991) Inhibition of cochlear hair cells by acetylcholine.J. Gen. Physiol. 98, 28a.

    Google Scholar 

  77. Fuchs P. A. and Murrow B. W. (1992) Cholinergic inhibition of short (outer) hair cells of the chick's cochlea.J. Neurosci. 12, 800–809.

    PubMed  CAS  Google Scholar 

  78. Tokimasa T. and North R. A. (1984) Calcium entry through acetylcholine channels can activate potassium conductance in bullfrog sympathetic neurons.Brain Res. 295, 364–367.

    Article  PubMed  CAS  Google Scholar 

  79. McEachern A. E., Margiotta J. F., and Berg D. K. (1985) Gamma-aminobutyric acid receptors on chick ciliary ganglion neurons in vivo and in cell culture.J. Neurosci. 5, 2690–2695.

    PubMed  CAS  Google Scholar 

  80. Wisgirda M. E. and Dryer S. E. (1994) Functional dependence of Ca2+-activated K+ current on L- and N-type Ca2+ channels: differences between chicken sympathetic and parasympathetic neurons suggest different regulatory mechanisms.Proc. Natl. Acad. Sci. USA 91, 2858–2862.

    Article  PubMed  CAS  Google Scholar 

  81. Wonnacott S., Drasdo A., Sanderson E., and Rowell P. (1990) Presynaptic nicotinic receptors and the modulation of transmission release, inThe Biology of Nicotine Dependence.Ciba Foundation Symposium (Block G. and Marsh J., eds.), Wiley, Chichester, NY, pp. 87–105.

    Chapter  Google Scholar 

  82. McGehee D. S., Heath M. J. S., Gelber S., Devay P., and Role L. W. (1995) Nicotine activation of presynaptic receptors on CNS neurons enhances fast excitatory synaptic transmission.Science 269, 1692–1696.

    Article  PubMed  CAS  Google Scholar 

  83. Pugh P. C. and Berg D. K. (1994) Neuronal acetylcholine receptors that bind α-bungarotoxin mediate neurite retraction in a calcium-dependent manner.J. Neurosci. 14, 889–896.

    PubMed  CAS  Google Scholar 

  84. Vijayaraghavan S., Huang B., Blumenthal E. M., and Berg D. K. (1995) Arachidonic acid as a possible negative feedback inhibitor of nicotinic acetylcholine receptors on neurons.J. Neurosci. 15, 3679–3687.

    PubMed  CAS  Google Scholar 

  85. Ehrengruber M. U. and Zahler P. (1991) Inhibition of the nicotinic ion channel by arachidonic acid and other unsaturated fatty acids in chromaffin cells from bovine adrenal medulla.Chimia 45, 45–49.

    CAS  Google Scholar 

  86. Ehrengruber M. U., Deranleau D. A., Kempf C., Zahler P., and Lanzrein M. (1993) Arachidonic acid and other unsaturated fatty acids alter membrane potential in PC12 and bovine adrenal chromaffin cells.J. Neurochem. 60, 282–288.

    Article  PubMed  CAS  Google Scholar 

  87. Legendre P., Rosenmund C., and Westbrook G. L. (1993) Inactivation of NMDA channels in cultured hippocampal neurons by intracellular calcium.J. Neurosci. 13, 674–684.

    PubMed  CAS  Google Scholar 

  88. Rosenmund C. and Westbrook G. L. (1993) Calcium-induced actin depolymerization reduces NMDA channel activity.Neuron 10, 805–814.

    Article  PubMed  CAS  Google Scholar 

  89. MacNicol M. and Schulman H. (1992) Multiple Ca2+ signalling pathways converge on CaM kinase in PC12 cells.FEBS Lett. 304, 237–240.

    Article  PubMed  CAS  Google Scholar 

  90. Rosen L. B., Ginty D. D., and Greenberg M. E. (1995) Calcium regulation of gene expression.Adv. Second Mess. Phosphoprotein Res. 30, 225–253.

    CAS  Google Scholar 

  91. Lerea L. S. and McNamara J. O. (1993) Ionotropic glutamate receptor subtypes activate c-fos transcription by distinct calcium-requiring intracellular signaling pathways.Neuron 10, 31–41.

    Article  PubMed  CAS  Google Scholar 

  92. Warburton D. M. (1992) Nicotine as a cognitive enhancer.Prog. Neuro-Psychopharmacol. Biol. Psych. 16, 181–191.

    Article  CAS  Google Scholar 

  93. Jarvik M. E. (1991) Beneficial effects of nicotine.Br. J. Addict. 86, 571–575.

    Article  PubMed  CAS  Google Scholar 

  94. Lee P. N. (1994) Smoking and Alzheimer's disease: a review of the epidemiological evidence.Neuroepidemiology 13, 131–144.

    Article  PubMed  Google Scholar 

  95. Schroder H., Giacobini E., Wevers A., Birtsch C., and Schutz U. (1995) Nicotinic receptors in Alzheimer's disease, inBrain Imaging of Nicotine and Tobacco Smoking (Domino E. F., ed.), NPP Books, Ann Arbor, MI, pp. 73–93.

    Google Scholar 

  96. Lippa A. S., Pelham R. W., Beer B., Critehett D. J., Dean R. I., and Bartus R. T. (1980) Brain cholinergic dysfunction and memory in aging rats.Neurobiol. Aging 1, 13–19.

    Article  PubMed  CAS  Google Scholar 

  97. Vinogradova O. (1975) Functional organization of the limbic system in the process of registration of information: facts and hypotheses, inThe Hippocampus: Neurophysiology and Behavior, vol. 2 (Isaacson R. L. and Pribram K. H., eds.), Plenum, New York, pp. 1–70.

    Google Scholar 

  98. Green R. C., Blume S. W., Kupferschmid S. B., and Mesulam M. M. (1989) Alterations of hippocampal acetylcholine esterase in human temporal lobe epilepsy.Ann. Neurol. 26, 347–351.

    Article  PubMed  CAS  Google Scholar 

  99. Marks M. J., Romm E., Campbell S. M., and Collins A. C. (1989) Variation of nicotinic binding sites among inbred strains.Pharmacol. Biochem. Behav. 33, 679–689.

    Article  PubMed  CAS  Google Scholar 

  100. Miner L. L. and Collins A. C. (1989) Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors.Pharmacol. Biochem. Behav. 33, 679–689.

    Article  Google Scholar 

  101. Luntz-Leybman V., Bickford P. C., and Freedman R. (1992) Cholinergic gating of response to auditory stimuli in rat hippocampus.Brain Res. 587, 130–136.

    Article  PubMed  CAS  Google Scholar 

  102. Picciotto M. R., Zoli M., Lena C., Bessis A., Lallemand Y., LeNovere N., Vincent P., Merlo Pich E., Brulet P., and Changeux J.-P. (1995) Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain.Nature 374, 65–67.

    Article  PubMed  CAS  Google Scholar 

  103. O'Sullivan A. J., Cheek T. R., Moreton R. B., Berridge M. J., and Burgoyne R. D. (1989) Localization and heterogeneity of agonist-induced changes in cytosolic calcium concentration in single bovine adrenal chromaffin cells from video imaging of fura-2.EMBO 8, 401–411.

    Google Scholar 

  104. Mueller W. and Connor J. A. (1991) Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses.Nature 354, 73–76.

    Article  Google Scholar 

  105. Regehr W. G. and Tank D. W. (1994) Dendritic calcium dynamics.Curr. Opin. Neurobiol. 4, 373–382.

    Article  PubMed  CAS  Google Scholar 

  106. Goldbeter A., Dupont G., and Berridge M. J. (1990) Minimal model for signal-induced Ca2+ oscillations and for their frequency encoding through protein phosphorylation.Development 87, 1461–1465.

    CAS  Google Scholar 

  107. Hanson P. I., Meyer T., Stryer L., and Schulman H. (1994) Dual role of calmodulin in autophosphorylation of multifunctional CaM kinase may underlie decoding of calcium signals.Neuron 12, 943–956.

    Article  PubMed  CAS  Google Scholar 

  108. Rosen L. B., Ginty D. D., Weber M. J., and Greenberg M. E. (1994) Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of rats.Neuron 12, 1207–1221.

    Article  PubMed  CAS  Google Scholar 

  109. Malenka R. C., Lancaster B., and Zucker R. S. (1992) Temporal limits on the rise in postsynaptic calcium required for the induction of long-term potentiation.Neuron 9, 121–128.

    Article  PubMed  CAS  Google Scholar 

  110. Mulkey R. M. and Malenka R. C. (1992) Mechanisms underlying induction of homosynaptic long-term depression in area CA1 of the hippocampus.Neuron 9, 967–975.

    Article  PubMed  CAS  Google Scholar 

  111. Fields R. D. and Nelson P. G. (1994) Resonant activation of calcium signal transduction in neurons.J. Neurobiol. 25, 281–293.

    Article  PubMed  CAS  Google Scholar 

  112. Gu X., Olson E. C., and Spitzer N. C. (1994) Spontaneous neuronal calcium spikes and waves during early differentiation.J. Neurosci. 14, 6325–6335.

    PubMed  CAS  Google Scholar 

  113. Gu X. and Spitzer N. C. (1995) Distinct aspects of neuronal differentiation encoded by frequency of spontaneous Ca2+ transients.Nature 375, 784–787.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rathouz, M.M., Vijayaraghavan, S. & Berg, D.K. Elevation of intracellular calcium levels in neurons by nicotinic acetylcholine receptors. Mol Neurobiol 12, 117–131 (1996). https://doi.org/10.1007/BF02740649

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02740649

Index Entries

Navigation