European Biophysics Journal

, Volume 34, Issue 8, pp 1007–1016 | Cite as

A simulation study on the Ca2+-independent but voltage-dependent exocytosis and endocytosis in dorsal root ganglion neurons

  • Hua Yang
  • Chen Zhang
  • Hui Zheng
  • Wei Xiong
  • Zhuan Zhou
  • Tao Xu
  • Jiu Ping Ding


In patch-clamped somata of dorsal root ganglion (DRG) neurons, two types of secretion have been proposed: Ca2+-dependent secretion and Ca2+-independent but voltage-dependent secretion (CIVDS). The Ca2+-induced and the depolarization-induced membrane capacitance (Cm) increases contribute 80 and 20% to the total Cm increase, respectively (Zhang and Zhou in Nat Neurosci 5:425, 2002). In order to explore the mechanism of the voltage-dependent Cm change (ΔCm), we constructed a model with sequential states. The simulation with this model closely approximates all the experimental data. The model predicts that the majority of fusion events (approximately 80%) are so-called “kiss-and-run” events, which account for the fast recovery or the rapid retrieval feature of the signals. The remaining 20% are attributed to full fusion events, which account for a slow retrieval feature. On the basis of the model, one mechanism of the activity-dependent endocytosis has revealed a differential distribution of vesicles between the kiss-and-run and full fusion states at different stimulation frequencies. The quantitative model presented in this study may help us to understand the mechanism of the CIVDS and the tightly coupled endocytosis found in mammalian DRG neurons.


Exocytosis Endocytosis Ca2+-independent but voltage-dependent secretion Capacitance Vesicle 



We thank Chris Lingle, Steven Mennerick and Iain Bruce for comments on the manuscript. This work was supported by grants from the National Science Foundation of China (30025023, 3000062 30130230, 30328013 and 30330210), the Major State Basic Research Program of the P.R. China (G1999054000, 2001CCA04100 and G2000077800), the Li Foundation and the Sinogerman Scientific Center.


  1. Aravanis AM, Pyle JL, Harata NC, Tsien RW (2003) Imaging single synaptic vesicles undergoing repeated fusion events: kissing, running, and kissing again. Neuropharmacology 45:797–813Google Scholar
  2. Augustine GJ, Charlton MP, Smith SJ (1987) Calcium action in synaptic transmitter release. Annu Rev Neurosci 10:633–693CrossRefPubMedGoogle Scholar
  3. Ben Chaim Y, Tour O, Dascal N, Parnas I, Parnas H (2003) The M2 muscarinic G-protein-coupled receptor is voltage-sensitive. J Biol Chem 278:22482–22491Google Scholar
  4. Bradley SR, Marino MJ, Wittmann M, Rouse ST, Awad H, Levey AI, Conn PJ (2000) Activation of group II metabotropic glutamate receptors inhibits synaptic excitation of the substantia Nigra pars reticulata. J Neurosci 20:3085–3094Google Scholar
  5. Erying (1935) Ionic channels of excitable membranes. BookGoogle Scholar
  6. Gillis KD (1995) Techniques for membrane capacitance measurements. In: Single channel recording, 2nd edn. pp 155–198Google Scholar
  7. Gillis KD, Mossner R, Neher E (1996) Protein kinase C enhances exocytosis from chromaffin cells by increasing the size of the readily releasable pool of secretory granules. Neuron 16:1209–1220CrossRefPubMedGoogle Scholar
  8. Harata N, Pyle JL, Aravanis AM, Mozhayeva M, Kavalali ET, Tsien RW (2001) Limited numbers of recycling vesicles in small CNS nerve terminals: implications for neural signaling and vesicular cycling. Trends Neurosci 24:637–643CrossRefPubMedGoogle Scholar
  9. Heinemann C, von Ruden L, Chow RH, Neher E (1993) A two-step model of secretion control in neuroendocrine cells. Pflugers Arch 424:105–112CrossRefPubMedGoogle Scholar
  10. Heinemann C, Chow RH, Neher E, Zucker RS (1994) Kinetics of the secretory response in bovine chromaffin cells following flash photolysis of caged Ca2+. Biophys J 67:2546–2557PubMedGoogle Scholar
  11. Hirose H, Seto Y, Maruyama H, Dan K, Nakamura K, Saruta T (1997) Effects of alpha 2-adrenergic agonism, imidazolines, and G-protein on insulin secretion in beta cells. Metabolism 46:1146–1149CrossRefPubMedGoogle Scholar
  12. Hochner B, Parnas H, Parnas I (1989) Membrane depolarization evokes neurotransmitter release in the absence of calcium entry. Nature 342:433–435Google Scholar
  13. Iino S, Sudo T, Niwa T, Fukasawa T, Hidaka H, Niki I (2000) Annexin XI may be involved in Ca2+—or GTP-gammaS-induced insulin secretion in the pancreatic beta-cell. FEBS Lett 479:46–50CrossRefPubMedGoogle Scholar
  14. Jahn R, Lang T, Sudhof TC (2003) Membrane fusion. Cell 112:519–533CrossRefPubMedGoogle Scholar
  15. Katz B (1969) The release of neural transmitter substances. Thomas, SpringfieldGoogle Scholar
  16. Klockner U, Lee JH, Cribbs LL, Daud A, Hescheler J, Pereverzev A, Perez-Reyes E, Schneider T (1999) Comparison of the Ca2 + currents induced by expression of three cloned alpha1 subunits, alpha1G, alpha1H and alpha1I, of low-voltage-activated T-type Ca2+ channels. Eur J Neurosci 11:4171–4178Google Scholar
  17. Leenders AG, Scholten G, de Lange RP, Lopes da Silva FH, Ghijsen WE (2002) Sequential changes in synaptic vesicle pools and endosome-like organelles during depolarization near the active zone of central nerve terminals. Neuroscience 109:195–206Google Scholar
  18. Llinas RR (1977) Depolarization-release coupling systems in neurons. Neurosci Res Program Bull 15:555–687PubMedGoogle Scholar
  19. Mochida S, Yokoyama CT, Kim DK, Itoh K, Catterall WA (1998) Evidence for a voltage-dependent enhancement of neurotransmitter release mediated via the synaptic protein interaction site of N-type Ca2+ channels. Proc Natl Acad Sci USA 95:14523–14528CrossRefPubMedGoogle Scholar
  20. Parnas H, Valle-Lisboa JC, Segel LA (2002) Can the Ca2+ hypothesis and the Ca2+-voltage hypothesis for neurotransmitter release be reconciled? Proc Natl Acad Sci USA 99:17149–17154CrossRefPubMedGoogle Scholar
  21. Richards DA, Guatimosim C, Betz WJ (2000) Two endocytic recycling routes selectively fill two vesicle pools in frog motor nerve terminals. Neuron 27:551–559CrossRefPubMedGoogle Scholar
  22. Richards DA, Guatimosim C, Rizzoli SO, Betz WJ (2003) Synaptic vesicle pools at the frog neuromuscular junction. Neuron 39:529–541CrossRefPubMedGoogle Scholar
  23. Sheng ZH, Rettig J, Cook T, Catterall WA (1996) Calcium-dependent interaction of N-type calcium channels with the synaptic core complex. Nature 379:451–454Google Scholar
  24. Silinsky EM, Watanabe M, Redman RS, Qiu R, Hirsh JK, Hunt JM, Solsona CS, Alford S, MacDonald RC (1995) Neurotransmitter release evoked by nerve impulses without Ca2+ entry through Ca2+ channels in frog motor nerve endings. J Physiol 482(Pt 3):511–520Google Scholar
  25. Slutsky I, Parnas H, Parnas I (1999) Presynaptic effects of muscarine on ACh release at the frog neuromuscular junction. J Physiol 514(Pt 3):769–782Google Scholar
  26. Sudhof TC (2000) The synaptic vesicle cycle revisited. Neuron 28:317–320CrossRefPubMedGoogle Scholar
  27. Sun JY, Wu XS, Wu LG (2002) Single and multiple vesicle fusion induce different rates of endocytosis at a central synapse. Nature 417:555–559Google Scholar
  28. Tsuboi T, Rutter GA (2003) Insulin secretion by ‘kiss-and-run’ exocytosis in clonal pancreatic islet beta-cells. Biochem Soc Trans 31:833–836CrossRefPubMedGoogle Scholar
  29. Voets T, Neher E, Moser T (1999) Mechanisms underlying phasic and sustained secretion in chromaffin cells from mouse adrenal slices. Neuron 23:607–615CrossRefPubMedGoogle Scholar
  30. Wang CT, Lu JC, Bai J, Chang PY, Martin TF, Chapman ER, Jackson MB (2003) Different domains of synaptotagmin control the choice between kiss-and-run and full fusion. Nature 424:943–947Google Scholar
  31. Wu LG (2004) Kinetic regulation of vesicle endocytosis at synapses. Trends Neurosci 27:548–554CrossRefPubMedGoogle Scholar
  32. Xu T, Binz T, Niemann H, Neher E (1998) Multiple kinetic components of exocytosis distinguished by neurotoxin sensitivity. Nat Neurosci 1:192–200Google Scholar
  33. Zhang C, Zhou Z (2002) Ca(2+)-independent but voltage-dependent secretion in mammalian dorsal root ganglion neurons. Nat Neurosci 5:425–430Google Scholar
  34. Zhang X, Aman K, Hokfelt T (1995) Secretory pathways of neuropeptides in rat lumbar dorsal root ganglion neurons and effects of peripheral axotomy. J Comp Neurol 352:481–500CrossRefPubMedGoogle Scholar
  35. Zhang C, Xiong W, Zheng H, Wang L, Lu B, Zhou Z (2004) Calcium- and dynamin-independent endocytosis in dorsal root ganglion neurons. Neuron 42:225–236CrossRefPubMedGoogle Scholar
  36. Zhu HL, Hille B, Xu T (2002) Sensitization of regulated exocytosis by protein kinase C. Proc Natl Acad Sci USA 99:17055–17059CrossRefPubMedGoogle Scholar
  37. Zucker RS (1996) Exocytosis: a molecular and physiological perspective. Neuron 17:1049–1055CrossRefPubMedGoogle Scholar

Copyright information

© EBSA 2005

Authors and Affiliations

  • Hua Yang
    • 1
  • Chen Zhang
    • 4
  • Hui Zheng
    • 3
    • 4
  • Wei Xiong
    • 3
    • 4
  • Zhuan Zhou
    • 3
    • 4
  • Tao Xu
    • 1
    • 2
  • Jiu Ping Ding
    • 1
  1. 1.Institute of Biophysics and Biochemistry, College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhanChina
  2. 2.National Laboratory of Biomacromolecules, Institute of BiophysicsChinese Academy of SciencesShanghaiChina
  3. 3.Institute of Molecular MedicinePeking UniversityBeijingChina
  4. 4.Institute of Neuroscience, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina

Personalised recommendations