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. 1995 Jul 18;92(15):6896–6900. doi: 10.1073/pnas.92.15.6896

The kinetics of quantal transmitter release from retinal amacrine cells.

S Borges 1, E Gleason 1, M Turelli 1, M Wilson 1
PMCID: PMC41437  PMID: 7624339

Abstract

Exocytosis of transmitter at most synapses is a very fast process triggered by the entry of Ca2+ during an action potential. A reasonable expectation is that the fast step of exocytosis is followed by slow steps readying another vesicle for exocytosis but the identity and kinetics of these steps are presently unclear. By voltage clamping both pre- and postsynaptic neurons in an isolated pair of retinal amacrine cells, we have measured evoked synaptic currents and responses to single vesicles of transmitter (minis). From these currents, we have computed the rate of exocytosis during a sustained presynaptic depolarization. We show here that for these cells, release is consistent with a scheme of "fire and reload." Large Ca2+ influx causes the rapid release of a small number of vesicles, typically approximately 10 per presynaptic neuron, likely corresponding to those vesicles already docked. After this spike of exocytosis whose peak is 150 quanta per release site per s, continued Ca2+ influx sustains release at only 22 quanta per release site per s, probably rate-limited by the docking of fresh vesicles.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Almers W. Synapses. How fast can you get? Nature. 1994 Feb 24;367(6465):682–683. doi: 10.1038/367682a0. [DOI] [PubMed] [Google Scholar]
  2. Barrett E. F., Stevens C. F. The kinetics of transmitter release at the frog neuromuscular junction. J Physiol. 1972 Dec;227(3):691–708. doi: 10.1113/jphysiol.1972.sp010054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bekkers J. M., Richerson G. B., Stevens C. F. Origin of variability in quantal size in cultured hippocampal neurons and hippocampal slices. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5359–5362. doi: 10.1073/pnas.87.14.5359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Celentano J. J., Wong R. K. Multiphasic desensitization of the GABAA receptor in outside-out patches. Biophys J. 1994 Apr;66(4):1039–1050. doi: 10.1016/S0006-3495(94)80885-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dempster J. The use of the driving function in the analysis of endplate current kinetics. J Neurosci Methods. 1986 Nov;18(3):277–285. doi: 10.1016/0165-0270(86)90014-2. [DOI] [PubMed] [Google Scholar]
  6. Edwards F. A., Konnerth A., Sakmann B. Quantal analysis of inhibitory synaptic transmission in the dentate gyrus of rat hippocampal slices: a patch-clamp study. J Physiol. 1990 Nov;430:213–249. doi: 10.1113/jphysiol.1990.sp018289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FATT P., KATZ B. Spontaneous subthreshold activity at motor nerve endings. J Physiol. 1952 May;117(1):109–128. [PMC free article] [PubMed] [Google Scholar]
  8. Faber D. S., Young W. S., Legendre P., Korn H. Intrinsic quantal variability due to stochastic properties of receptor-transmitter interactions. Science. 1992 Nov 27;258(5087):1494–1498. doi: 10.1126/science.1279813. [DOI] [PubMed] [Google Scholar]
  9. Fernandez J. M., Neher E., Gomperts B. D. Capacitance measurements reveal stepwise fusion events in degranulating mast cells. 1984 Nov 29-Dec 5Nature. 312(5993):453–455. doi: 10.1038/312453a0. [DOI] [PubMed] [Google Scholar]
  10. Gleason E., Borges S., Wilson M. Control of transmitter release from retinal amacrine cells by Ca2+ influx and efflux. Neuron. 1994 Nov;13(5):1109–1117. doi: 10.1016/0896-6273(94)90049-3. [DOI] [PubMed] [Google Scholar]
  11. Gleason E., Borges S., Wilson M. Synaptic transmission between pairs of retinal amacrine cells in culture. J Neurosci. 1993 Jun;13(6):2359–2370. doi: 10.1523/JNEUROSCI.13-06-02359.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gleason E., Mobbs P., Nuccitelli R., Wilson M. Development of functional calcium channels in cultured avian photoreceptors. Vis Neurosci. 1992 Apr;8(4):315–327. doi: 10.1017/s0952523800005058. [DOI] [PubMed] [Google Scholar]
  13. Goda Y., Stevens C. F. Two components of transmitter release at a central synapse. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12942–12946. doi: 10.1073/pnas.91.26.12942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Greengard P., Valtorta F., Czernik A. J., Benfenati F. Synaptic vesicle phosphoproteins and regulation of synaptic function. Science. 1993 Feb 5;259(5096):780–785. doi: 10.1126/science.8430330. [DOI] [PubMed] [Google Scholar]
  15. Heidelberger R., Heinemann C., Neher E., Matthews G. Calcium dependence of the rate of exocytosis in a synaptic terminal. Nature. 1994 Oct 6;371(6497):513–515. doi: 10.1038/371513a0. [DOI] [PubMed] [Google Scholar]
  16. Heinemann C., von Rüden L., Chow R. H., Neher E. A two-step model of secretion control in neuroendocrine cells. Pflugers Arch. 1993 Jul;424(2):105–112. doi: 10.1007/BF00374600. [DOI] [PubMed] [Google Scholar]
  17. Hessler N. A., Shirke A. M., Malinow R. The probability of transmitter release at a mammalian central synapse. Nature. 1993 Dec 9;366(6455):569–572. doi: 10.1038/366569a0. [DOI] [PubMed] [Google Scholar]
  18. Horn R., Marty A. Muscarinic activation of ionic currents measured by a new whole-cell recording method. J Gen Physiol. 1988 Aug;92(2):145–159. doi: 10.1085/jgp.92.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Katz B., Miledi R. The effect of temperature on the synaptic delay at the neuromuscular junction. J Physiol. 1965 Dec;181(3):656–670. doi: 10.1113/jphysiol.1965.sp007790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Korn H., Faber D. S. Quantal analysis and synaptic efficacy in the CNS. Trends Neurosci. 1991 Oct;14(10):439–445. doi: 10.1016/0166-2236(91)90042-s. [DOI] [PubMed] [Google Scholar]
  21. Maconochie D. J., Zempel J. M., Steinbach J. H. How quickly can GABAA receptors open? Neuron. 1994 Jan;12(1):61–71. doi: 10.1016/0896-6273(94)90152-x. [DOI] [PubMed] [Google Scholar]
  22. Mandell J. W., Townes-Anderson E., Czernik A. J., Cameron R., Greengard P., De Camilli P. Synapsins in the vertebrate retina: absence from ribbon synapses and heterogeneous distribution among conventional synapses. Neuron. 1990 Jul;5(1):19–33. doi: 10.1016/0896-6273(90)90030-j. [DOI] [PubMed] [Google Scholar]
  23. Monck J. R., Robinson I. M., Escobar A. L., Vergara J. L., Fernandez J. M. Pulsed laser imaging of rapid Ca2+ gradients in excitable cells. Biophys J. 1994 Aug;67(2):505–514. doi: 10.1016/S0006-3495(94)80554-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Neher E., Marty A. Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6712–6716. doi: 10.1073/pnas.79.21.6712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Neher E., Zucker R. S. Multiple calcium-dependent processes related to secretion in bovine chromaffin cells. Neuron. 1993 Jan;10(1):21–30. doi: 10.1016/0896-6273(93)90238-m. [DOI] [PubMed] [Google Scholar]
  26. Parsons T. D., Lenzi D., Almers W., Roberts W. M. Calcium-triggered exocytosis and endocytosis in an isolated presynaptic cell: capacitance measurements in saccular hair cells. Neuron. 1994 Oct;13(4):875–883. doi: 10.1016/0896-6273(94)90253-4. [DOI] [PubMed] [Google Scholar]
  27. Rieke F., Schwartz E. A. A cGMP-gated current can control exocytosis at cone synapses. Neuron. 1994 Oct;13(4):863–873. doi: 10.1016/0896-6273(94)90252-6. [DOI] [PubMed] [Google Scholar]
  28. Roberts W. M. Localization of calcium signals by a mobile calcium buffer in frog saccular hair cells. J Neurosci. 1994 May;14(5 Pt 2):3246–3262. doi: 10.1523/JNEUROSCI.14-05-03246.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rosenmund C., Clements J. D., Westbrook G. L. Nonuniform probability of glutamate release at a hippocampal synapse. Science. 1993 Oct 29;262(5134):754–757. doi: 10.1126/science.7901909. [DOI] [PubMed] [Google Scholar]
  30. Thomas P., Surprenant A., Almers W. Cytosolic Ca2+, exocytosis, and endocytosis in single melanotrophs of the rat pituitary. Neuron. 1990 Nov;5(5):723–733. doi: 10.1016/0896-6273(90)90226-6. [DOI] [PubMed] [Google Scholar]
  31. Thomas P., Wong J. G., Lee A. K., Almers W. A low affinity Ca2+ receptor controls the final steps in peptide secretion from pituitary melanotrophs. Neuron. 1993 Jul;11(1):93–104. doi: 10.1016/0896-6273(93)90274-u. [DOI] [PubMed] [Google Scholar]
  32. Van der Kloot W. Estimating the timing of quantal releases during end-plate currents at the frog neuromuscular junction. J Physiol. 1988 Aug;402:595–603. doi: 10.1113/jphysiol.1988.sp017224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Verdoorn T. A., Draguhn A., Ymer S., Seeburg P. H., Sakmann B. Functional properties of recombinant rat GABAA receptors depend upon subunit composition. Neuron. 1990 Jun;4(6):919–928. doi: 10.1016/0896-6273(90)90145-6. [DOI] [PubMed] [Google Scholar]
  34. von Gersdorff H., Matthews G. Dynamics of synaptic vesicle fusion and membrane retrieval in synaptic terminals. Nature. 1994 Feb 24;367(6465):735–739. doi: 10.1038/367735a0. [DOI] [PubMed] [Google Scholar]
  35. von Rüden L., Neher E. A Ca-dependent early step in the release of catecholamines from adrenal chromaffin cells. Science. 1993 Nov 12;262(5136):1061–1065. doi: 10.1126/science.8235626. [DOI] [PubMed] [Google Scholar]

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