Calcium and neuronal function

Abstract

Calcium is unique among metals because its ions have a very large concentration gradient across the plasma membrane of all cells, from 10−3 M Ca2+ outside, to 10−7 M Ca2+ inside. This gradient is maintained by the use of metabolic energy through ion pumping, and its existence allows cells to use transient increases in the intracellular Ca2+ concentration as signals, which regulate cell function. In neurones these Ca signals are initiated by electrical activity (action potentials) which open voltage-dependent Ca channels in the plasma membrane, allowing Ca to enter the cell. Intracellular Ca signals can also be produced by transmitters at synapses, which open Ca channels, either directly, or indirectly by causing local depolarization and the opening of voltage-dependent Ca channels. The main effects of Ca signals on neurones are to alter their electrical activity, by modifying the opening and closing of Na and K channels, and to stimulate the release of transmitter substance. Ca has a host of other effects, such as the regulation of metabolic activity, the regulation of cell growth, and the long-term modification of synaptic efficiency, and it is even implicated in the destruction of neurones.

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

References

  1. [1]

    Abrams TW, ER Kandel: Is contiguity detection in classical conditioning a system or a cellular property? Trends in Neurosci 11 (1988) 128–135

    Google Scholar 

  2. [2]

    Åkerman Keo, DG Nicholls: Physiological and bioenergetic aspects of mitochondrial calcium transport. Rev Physiol Biochem Pharmacol 95 (1983) 149–201

    Google Scholar 

  3. [3]

    Alvarez-Leefmans FJ, TJ Rink, RY Tsien: Free calcium ions in neurones ofhelix aspersa measured with ion-selective micro-electrodes. J Physiol (Lond) 315 (1981) 531–548

    Google Scholar 

  4. [4]

    Andrews SB, RD Leapman, DMD Landis, TS Reese: Distribution of calcium and potassium in presynaptic nerve terminals from cerebellar cortex. Proc Natl Acad Sci USA 84 (1987) 1713–1717

    PubMed  Google Scholar 

  5. [5]

    Andrews SB, RD Leapman, DMD Landis, TS Reese: Activity-dependent accumulation of calcium in purkinje cell dendritic spines. Proc Natl Acad Sci USA 85 (1988) 1682–1685

    PubMed  Google Scholar 

  6. [6]

    Armstrong CM, DR Matteson: The role of calcium ions in the closing of K channels. J Gen Physiol 87 (1986) 817–832

    PubMed  Google Scholar 

  7. [7]

    Ascher P, L Nowak: The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture. J Physiol (Lond) 399 (1988) 247–266

    Google Scholar 

  8. [8]

    Augustine GJ, MP Charlton, SJ Smith: Calcium entry into voltage-clamped presynaptic terminals of squid. J Physiol (Lond) 367 (1985) 143–162

    Google Scholar 

  9. [9]

    Augustine GJ, MP Charlton, SJ Smith: Calcium action in synaptic transmitter release. Annu Rev Neurosci 10 (1987) 633–693

    PubMed  Google Scholar 

  10. [10]

    Baimbridge KG, JJ Miller, CO Parkes: Calciumbinding protein distribution in the rat brain. Brain Res 239 (1982) 519–525

    PubMed  Google Scholar 

  11. [11]

    Baker PF: Transport and metabolism of calcium ions in nerve. Prog Biophys Mol Biol 24 (1972) 177–223

    PubMed  Google Scholar 

  12. [12]

    Baker PF, R Dipolo: Axonal calcium and magnesium homeostasis. Curr Top Membr Transp 22 (1984) 195–247

    Google Scholar 

  13. [13]

    Baker, PF, AL Hodgkin, EB Ridgway: Depolarization and calcium entry in squid giant axons. J Physiol (Lond) 218 (1971) 709–755

    Google Scholar 

  14. [14]

    Baker PF, JA Umbach: Calcium buffering in axons and axoplasm of loligo. J Physiol (Lond) 383 (1987) 369–394

    Google Scholar 

  15. [15]

    Berridge MJ, RF Irvine: Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312 (1984) 315–321

    PubMed  Google Scholar 

  16. [16]

    Blatz AL, KL Magleby: Calcium-activated potassium channels. Trends in Neurosci 11 (1987) 463–467

    Google Scholar 

  17. [17]

    Blaustein MP: Calcium and synaptic function. Handb Exp Pharmacol 83 (1988) 275–304

    Google Scholar 

  18. [18]

    Bradbury M: The Concept of a Blood-Brain Barrier. John Wiley & Sons, Chichester 1979

    Google Scholar 

  19. [19]

    Campbell AK: Intracellular calcium. John Wiley & Sons, Chichester 1983

    Google Scholar 

  20. [20]

    Carbone E, HD Lux: Kinetics and selectivity of a low-voltage-activated calcium current in chick and rat sensory neurones. J Physiol (Lond) 386 (1987) 547–570

    Google Scholar 

  21. [21]

    Celio MR: Parvalbumin in most γ-aminobutyric acidcontaining neurons of the rat cerebral cortex. Science 231 (1986) 995–997

    Google Scholar 

  22. [22]

    Choi DW: Ionic dependence of glutamate neurotoxicity. J Neurosci 7 (1987) 369–379

    PubMed  Google Scholar 

  23. [23]

    Cohan CS, JA Connor, SB Kater: Electrically and chemically mediated increases in intracellular Calcium in neuronal growth cones. J Neurosci 7 (1987) 3588–3599

    PubMed  Google Scholar 

  24. [24]

    Collingridge GL, TVP Bliss: NMDA receptors -their role in long-term potentiation. Trends in Neurosci 10 (1987) 288–293

    Google Scholar 

  25. [25]

    Coyle JT: Neurotoxic action of kainic acid. J Neurochem 41 (1983) 1–11

    PubMed  Google Scholar 

  26. [26]

    Douglas WW: Involvement of calcium in exocytosis and the exocytosis-vesiculation sequence. Biochem Soc Symp 39 (1974) 1–28

    PubMed  Google Scholar 

  27. [27]

    Drust DS, CE Creutz: Aggregation of chromaffin granules by calpactin at micromolar levels of calcium. Nature 331 (1988) 88–91

    PubMed  Google Scholar 

  28. [28]

    Farber JL: The role of calcium in cell death. Life Sci 29 (1981) 1289–1295

    PubMed  Google Scholar 

  29. [29]

    Fox AP, MC Nowycky, RW Tsien: Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J Physiol (Lond) 394 (1987) 149–172

    Google Scholar 

  30. [30]

    Frankenhaeuser B, AL Hodgkin: The action of calcium on the electrical properties of squid axons. J Physiol (Lond) 137 (1957) 218–244

    Google Scholar 

  31. [31]

    Gilly WF, CM Armstrong: Slowing of sodium channel opening kinetics in squid axon by extracellular zinc. J Gen Physiol 79 (1982) 935–964

    PubMed  Google Scholar 

  32. [32]

    Gorman Alf, A Hermann, MV Thomas: Ionic requirements for membrane oscillations and their dependence on the calcium concentration in a molluscan pace-maker neurone. J Physiol (Lond) 327 (1982) 185–217

    Google Scholar 

  33. [33]

    Gorman Alf, S Levy, E Nasi, D Tillotson: Intracellular calcium measured with calcium-sensitive micro-electrodes and arsenazo III in voltage-clampedaplysia neurones. J Physiol (Lond) 353 (1984) 127–142

    Google Scholar 

  34. [34]

    Gustafsson B, H Wigström: Physiological mechanisms underlying long-term potentiation. Trends in Neurosci 11 (1988) 156–162

    Google Scholar 

  35. [35]

    Hamill OP, A Marty, E Neher, B Sakmann, FJ Sigworth: Improved patch-clamp techniques for high-resolution current recording from cell and cell-free membrane patches. Pflugers Arch 391 (1981) 85–100

    PubMed  Google Scholar 

  36. [36]

    Hansen AJ, T Zeuthen: Extracellular ion concentrations during spreading depression and ischemia in the rat brain cortex. Acta Physiol Scand 113 (1981) 437–445

    PubMed  Google Scholar 

  37. [37]

    Heizmann CW: Parvalbumin, an intracellular calcium-binding protein: distribution, properties and possible role in mammalian cells. Experientia 40 (1984) 910–921

    PubMed  Google Scholar 

  38. [38]

    Heuser JE, TS Reese: Structural changes after transmitter release at the frog neuromuscular junction. J Cell Biol 88 (1981) 564–580

    PubMed  Google Scholar 

  39. [39]

    Hirning LD, AP Fox, EW McCleskey, BM Olivera, SA Thayer, RJ Miller, RW Tsien: Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons. Science 239 (1988) 57–61

    PubMed  Google Scholar 

  40. [40]

    Hodgkin AL: The conduction of the Nervous Impulse. Liverpool University Press, Liverpool 1964

    Google Scholar 

  41. [41]

    Hofmann F, W Nastainczyk, A Röhrkasten, T Schneider, M Sieber: Regulation of the L-type calcium channel. Trends in Pharmacol Sci 8 (1987) 393–398

    Google Scholar 

  42. [42]

    Jahnsen H, R Llinas: Ionic basis the electroresponsiveness and oscillatory properties of guinea-pig thalamic neuronesin vitro. J Physiol (Lond) 349 (1984) 227–247

    Google Scholar 

  43. [43]

    Kaczmarek LK: The role of protein kinase C in the regulation of ion channels and neurotransmitter release. Trends in Neurosci 10 (1987) 30–34

    Google Scholar 

  44. [44]

    Katz B: The release of neural transmitter substances. Liverpool University Press, Liverpool 1969

    Google Scholar 

  45. [45]

    King MM, CY Huang, PB Chock, AC Nairn, HC Hemmings, K-FJ Chan, P Greengard: Mammalian brain phosphoproteins as substrates for calcineurin. J Biol Chem 259 (1984) 8080–8083

    PubMed  Google Scholar 

  46. [46]

    Knight DE, PF Baker: Calcium-dependence of catecholamine release from bovine adrenal medullary cells after exposure to intense electric fields. J Membr Biol 68 (1982) 107–140

    PubMed  Google Scholar 

  47. [47]

    Knight DE, NT Kesteven: Evoked transient intracellular free Ca2+ changes and secretion in isolated bovine adrenal medullary cells. Proc R Soc Lond [Biol] 218 (1983) 177–199

    Google Scholar 

  48. [48]

    Kretsinger RH: The informational role of calcium in the cytosol. Adv Cyclic Nucleotide Res 11 (1979) 1–26

    PubMed  Google Scholar 

  49. [49]

    Kretz R, E Shapiro, ER Kandel: Post-tetanic potentiation at an identified synapse inAplysia is correlated with a Ca2+-activated K+ current in the presynaptic neuron: Evidence for Ca2+ accumulation. Proc Natl Acad Sci USA 79 (1982) 5430–5434

    PubMed  Google Scholar 

  50. [50]

    Kudo Y, K Ho, H Miyakawa, Y Izumi, A Ogura, H Kato: Cytoplasmic calcium elevation in hippocampal granule cell induced by perforant path stimulation and L-glutamate elevation. Brain Res 407 (1987) 168–172

    PubMed  Google Scholar 

  51. [51]

    Lauritzen M: Cortical spreading depression as a putative migraine mechanism. Trends in Neurosci 10 (1987) 8–12

    Google Scholar 

  52. [52]

    Lehmann A: Neurotoxicity of calcium ionophore A 23187 in immature rat cerebellar slices. Neurosci Lett 79 (1987) 263–266

    PubMed  Google Scholar 

  53. [53]

    Llinas R, C Nicholson: Calcium role in depolarization-secretion coupling: an aequorin study in squid giant synapse. Proc Natl Acad Sci USA 72 (1975) 187–190

    PubMed  Google Scholar 

  54. [54]

    Lynch G, M Baudry: The biochemistry of memory: a new and specific hypothesis. Science 224 (1984) 1057–1063

    PubMed  Google Scholar 

  55. [55]

    McBurney RN, IR Neering: Neuronal calcium homeostasis. Trends in Neurosci 10 (1987) 164–169

    Google Scholar 

  56. [56]

    McCormack JG, RM Denton: Ca2+ as a second messenger within mitochondria. Trends in Biochem Sci 11 (1986) 258–262

    Google Scholar 

  57. [57]

    Manalon AS, CB Klee: Calmodulin. Adv Cyclic Nucleotide Protein Phosphorylation Res. 18 (1984) 227–278

    PubMed  Google Scholar 

  58. [58]

    Mayer ML, GL Westbrook: Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones. J Physiol (Lond) 394 (1987) 501–527

    Google Scholar 

  59. [59]

    Miledi R, I Parker, G Schalow: Transmitter induced calcium entry across the post-synaptic membrane at frog end-plates measured using arsenazo III. J Physiol (Lond) 300 (1980) 197–212

    Google Scholar 

  60. [60]

    Miller RJ: How many types of calcium channels exist in neurones? Trends in Neurosci 8 (1985) 45–47

    Google Scholar 

  61. [61]

    Montarsolo PG, ER Kandel, S Shacher: Longterm heterosynaptic inhibition inaplysia. Nature 333 (1988) 171–174

    PubMed  Google Scholar 

  62. [62]

    Murphy TH, AT Malrouf, A Sastre, RL Schnaar, JT Coyle: Calcium-dependent glutamate cytotoxicity in a neuronal cell line. Brain Res 444 (1988) 325–332

    PubMed  Google Scholar 

  63. [63]

    Nestler EJ, P Greengard: Protein phosphorylation in the brain. Nature 305 (1983) 583–588

    PubMed  Google Scholar 

  64. [64]

    Nohmi M, K Kuba, A Ogura, Y Kudo: Measurement of intracellular Ca2+ in the bullfrog sympathetic ganglion cells using fura-2 fluorescence. Brain Res 438 (1988) 175–181

    PubMed  Google Scholar 

  65. [65]

    Nordmann JJ, J Chevallier: The role of microvesicles in buffering [Ca2+]i in the neurohypophysis. Nature 287 (1980) 54–58

    PubMed  Google Scholar 

  66. [66]

    Patridge LD, D Swandulla: Calcium-activated nonspecific cation channels. Trends in Neurosci 11 (1988) 69–72

    Google Scholar 

  67. [67]

    Perrin D, OK Langley, D Aunis: Anti-α-fodrin inhibits secretion from permeabilized chromaffin cells. Nature 326 (1987) 498–501

    PubMed  Google Scholar 

  68. [68]

    Pontremoli S, E Melloni: Extralysosomal protein degradation. Annu Rev Biochem 55 (1986) 455–481

    PubMed  Google Scholar 

  69. [69]

    Rasmussen H: Calcium and cAMP as synarchic messengers. Wiley-Interscience, New York 1981

    Google Scholar 

  70. [70]

    Reuter H: Calcium channel modulation by neurotransmitter, enzymes and drugs. Nature 301 (1983) 569–574

    PubMed  Google Scholar 

  71. [71]

    Ross WN, H Arechiga, JG Nicholls: Optical recording of calcium and voltage transients following impulses in cell bodies and processes of identified leech neurones in culture. J Neurosci 7 (1987) 3877–3887

    PubMed  Google Scholar 

  72. [72]

    Schatzmann HJ: The plasma membrane calcium pump of erythrocytes and other animal cells. In:Carafoli E (ed): Membrane Transport of Calcium. Academic Press, London 1982

    Google Scholar 

  73. [73]

    Storm JF: Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells. J Physiol (Lond) 385 (1987) 733–759

    Google Scholar 

  74. [74]

    Tanabe T, H Takeshima, A Mikami, V Flockerzi, H Takahashi, K Kangawa, M Kojima, H Matsuo, T Hirose, S Numa: Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature 328 (1987) 313–318

    PubMed  Google Scholar 

  75. [75]

    Teyler, TJ, P Discenna: Long-term potentiation. Annu Rev Neurosci 10 (1987) 131–161

    PubMed  Google Scholar 

  76. [76]

    Tsien RW: Calcium channels in excitable cell membranes. Annu Rev Physiol 45 (1983) 341–358

    PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Simons, T.J.B. Calcium and neuronal function. Neurosurg. Rev. 11, 119–129 (1988). https://doi.org/10.1007/BF01794675

Download citation

Keywords

  • Calcium
  • neurons
  • nervous system