Calcium dependence of the rate of exocytosis in a synaptic terminal


RAPID calcium-dependent exocytosis underlies neurotransmitter release from nerve terminals. Despite the fundamental importance of this process, neither the relationship between presynaptic intra-cellular calcium ion concentration ([Ca2+]i) and rate of exocytosis, nor the maximal rate of secretion is known quantitatively. To provide this information, we have used flash photolysis of caged Ca2+ to elevate [Ca2+]i rapidly and uniformly in synaptic terminals, while measuring membrane capacitance as an index of exocytosis and monitoring [Ca2+]i with a Ca2+-indicator dye. When [Ca2+]i was abruptly increased to >10 µM, capacitance rose at a rate that increased steeply with [Ca2+]i. The steepness suggested that at least four calcium ions must bind to activate synaptic vesicle fusion. Half-saturation was at 194 µM, and the maximal rate constant was 2,000–3,000 s–1. A given synaptic vesicle can exocytose with high probability within a few hundred microseconds, if [Ca2+]i rises above lOOµM. These properties provide for the extremely rapid signalling required for neuronal communication.

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  1. 1

    Ishida, A. T., Stell, W. K. & Lightfoot, D. O. J. comp. Neurol. 191, 315–355 (1980).

    CAS  Article  Google Scholar 

  2. 2

    Yazulla, S., Studholme, K. M. & Wu, J.-Y. Brain Res. 411, 400–405 (1987).

    CAS  Article  Google Scholar 

  3. 3

    von Gersdorff, H. & Matthews, G. Nature 367, 735–739 (1994).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Kaplan, J. H. & Ellis Davis, G. C. R. Proc. natn. Acad. Sci. U.S.A. 85, 6571–6575 (1988).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Konishi, M. S., Hollingworth, A. B. & Baylor, S. M. J. gen. Physiol. 97, 271–301 (1991).

    CAS  Article  Google Scholar 

  6. 6

    Dowling, J. E. in The Retina: An Approachable Part of the Brain 42–80 (Belknap Press, Cambridge MA, 1987).

    Google Scholar 

  7. 7

    Katz, B. & Miledi, R. Proc. R. Soc. B161, 483–495 (1965).

    ADS  Google Scholar 

  8. 8

    Delaney, K. R. & Zucker, R. S. J. Physiol., Lond. 425, 473–498 (1990).

    Article  Google Scholar 

  9. 9

    Llinas, R., Steinberg, I. Z. & Walton, K. Biophys. J. 33, 323–351 (1981).

    CAS  Article  Google Scholar 

  10. 10

    Almers, W. Nature 367, 682–683 (1994).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Parnas, H., Dudel, J. & Parnas, I. Pflügers Arch 406, 121–130 (1986).

    CAS  Article  Google Scholar 

  12. 12

    Thomas, P., Wong, J. G. & Almers, W. EMBO J. 12, 303–306 (1993).

    CAS  Article  Google Scholar 

  13. 13

    Thomas, P., Wong, J. G., Lee, A. K. & Almers, W. Neuron 11, 93–104 (1993).

    CAS  Article  Google Scholar 

  14. 14

    Heinemann, C., Chow, R. H., Neher, E. & Zucker, R. S. Biophys. J. (in the press).

  15. 15

    Roberts, W. M., Jacobs, R. A. & Hudspeth, A. J. J. Neurosci. 10, 3664–3684 (1990).

    CAS  Article  Google Scholar 

  16. 16

    Adler, E. M., Augustine, G. J., Duffy, S. N. & Charleton, M. P. J. Neurosci. 11, 1496–1507 (1991).

    CAS  Article  Google Scholar 

  17. 17

    Llinas, R., Sugimori, M. & Silver R. B. Science 256, 677–679 (1992).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Augustine, G. J. & Neher, E. J. Physiol., Lond. 450, 247–271 (1992).

    CAS  Article  Google Scholar 

  19. 19

    Simon, S. M. & Llinas, R. R. Biophys. J. 48, 485–498 (1985).

    ADS  CAS  Article  Google Scholar 

  20. 20

    Zucker, R. S. & Fogelson, A. L. Proc. natn. Acad. Sci. U.S.A. 83, 3032–3036 (1986).

    ADS  CAS  Article  Google Scholar 

  21. 21

    Chad, J. E. & Eckert, R. Biophys. J. 45, 993–999 (1984).

    ADS  CAS  Article  Google Scholar 

  22. 22

    Heidelberger, R. & Matthews, G. J. Physiol., Lond. 447, 235–256 (1992).

    CAS  Article  Google Scholar 

  23. 23

    Lindau, M. & Neher E. Pflügers Arch. 411, 137–146 (1988).

    CAS  Article  Google Scholar 

  24. 24

    Chow R. H., von Rüden, L. & Neher, E. Nature 356, 60–63 (1992).

    ADS  CAS  Article  Google Scholar 

  25. 25

    Herrington, J. & Bookman, R. J. PULSE CONTROL V3.0: IGOR XOPs for Patch Clamp Data Acquisition (University of Miami, Miami, 1993).

    Google Scholar 

  26. 26

    Zucker, R. S. Cell Calcium 14, 87–100 (1993).

    CAS  Article  Google Scholar 

  27. 27

    von Gersdorff, H. & Matthews, G. Nature 370, 652–655 (1994).

    ADS  CAS  Article  Google Scholar 

  28. 28

    Grynkiewicz, G. M., Poenie, M. & Tsien, R. Y. J. biol. Chem. 260, 3440–3450 (1985).

    CAS  Google Scholar 

  29. 29

    McCray, J., Fidler-Lim, N., Ellis-Davis, G. & Kaplan, J. H. Biochemistry 37, 8856–8861 (1992).

    Article  Google Scholar 

  30. 30

    Heinemann, C., von Rüden, L., Chow, R. H. & Neher, E. Pflügers Arch. 424, 105–112 (1993).

    CAS  Article  Google Scholar 

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Heidelberger, R., Heinemann, C., Neher, E. et al. Calcium dependence of the rate of exocytosis in a synaptic terminal. Nature 371, 513–515 (1994).

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