Skip to main content
Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 1999 Feb 28;354(1381):347–355. doi: 10.1098/rstb.1999.0386

Effect of changes in action potential shape on calcium currents and transmitter release in a calyx-type synapse of the rat auditory brainstem.

J G Borst 1, B Sakmann 1
PMCID: PMC1692496  PMID: 10212483

Abstract

We studied the relation between the size of presynaptic calcium influx and transmitter release by making simultaneous voltage clamp recordings from presynaptic terminals, the calyces of Held and postsynaptic cells, the principal cells of the medical nucleus of the trapezoid body, in slices of the rat brainstem. Calyces were voltage clamped with different action potential waveforms. The amplitude of the excitatory postsynaptic currents depended supralinearly on the size of the calcium influx, in the absence of changes in the time-course of the calcium influx. This result is in agreement with the view that at this synapse most vesicles are released by the combined action of multiple calcium channels.

Full Text

The Full Text of this article is available as a PDF (225.4 KB).

Selected References

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

  1. Adler E. M., Augustine G. J., Duffy S. N., Charlton M. P. Alien intracellular calcium chelators attenuate neurotransmitter release at the squid giant synapse. J Neurosci. 1991 Jun;11(6):1496–1507. doi: 10.1523/JNEUROSCI.11-06-01496.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Augustine G. J., Adler E. M., Charlton M. P. The calcium signal for transmitter secretion from presynaptic nerve terminals. Ann N Y Acad Sci. 1991;635:365–381. doi: 10.1111/j.1749-6632.1991.tb36505.x. [DOI] [PubMed] [Google Scholar]
  3. Augustine G. J., Charlton M. P. Calcium dependence of presynaptic calcium current and post-synaptic response at the squid giant synapse. J Physiol. 1986 Dec;381:619–640. doi: 10.1113/jphysiol.1986.sp016347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Augustine G. J., Charlton M. P., Smith S. J. Calcium entry and transmitter release at voltage-clamped nerve terminals of squid. J Physiol. 1985 Oct;367:163–181. doi: 10.1113/jphysiol.1985.sp015819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Augustine G. J., Eckert R. Divalent cations differentially support transmitter release at the squid giant synapse. J Physiol. 1984 Jan;346:257–271. doi: 10.1113/jphysiol.1984.sp015020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Augustine G. J. Regulation of transmitter release at the squid giant synapse by presynaptic delayed rectifier potassium current. J Physiol. 1990 Dec;431:343–364. doi: 10.1113/jphysiol.1990.sp018333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Banks M. I., Smith P. H. Intracellular recordings from neurobiotin-labeled cells in brain slices of the rat medial nucleus of the trapezoid body. J Neurosci. 1992 Jul;12(7):2819–2837. doi: 10.1523/JNEUROSCI.12-07-02819.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Barnes-Davies M., Forsythe I. D. Pre- and postsynaptic glutamate receptors at a giant excitatory synapse in rat auditory brainstem slices. J Physiol. 1995 Oct 15;488(Pt 2):387–406. doi: 10.1113/jphysiol.1995.sp020974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bennett M. K., Calakos N., Scheller R. H. Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science. 1992 Jul 10;257(5067):255–259. doi: 10.1126/science.1321498. [DOI] [PubMed] [Google Scholar]
  10. Bennett M. R., Brain K. Autonomic synaptic transmission at single boutons and calyces. J Neurocytol. 1997 Sep;26(9):577–603. doi: 10.1023/a:1018537625551. [DOI] [PubMed] [Google Scholar]
  11. Bezprozvanny I., Scheller R. H., Tsien R. W. Functional impact of syntaxin on gating of N-type and Q-type calcium channels. Nature. 1995 Dec 7;378(6557):623–626. doi: 10.1038/378623a0. [DOI] [PubMed] [Google Scholar]
  12. Borst J. G., Helmchen F. Calcium influx during an action potential. Methods Enzymol. 1998;293:352–371. doi: 10.1016/s0076-6879(98)93023-3. [DOI] [PubMed] [Google Scholar]
  13. Borst J. G., Helmchen F., Sakmann B. Pre- and postsynaptic whole-cell recordings in the medial nucleus of the trapezoid body of the rat. J Physiol. 1995 Dec 15;489(Pt 3):825–840. doi: 10.1113/jphysiol.1995.sp021095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Borst J. G., Sakmann B. Calcium current during a single action potential in a large presynaptic terminal of the rat brainstem. J Physiol. 1998 Jan 1;506(Pt 1):143–157. doi: 10.1111/j.1469-7793.1998.143bx.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Borst J. G., Sakmann B. Calcium influx and transmitter release in a fast CNS synapse. Nature. 1996 Oct 3;383(6599):431–434. doi: 10.1038/383431a0. [DOI] [PubMed] [Google Scholar]
  16. Chad J. E., Eckert R. Calcium domains associated with individual channels can account for anomalous voltage relations of CA-dependent responses. Biophys J. 1984 May;45(5):993–999. doi: 10.1016/S0006-3495(84)84244-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dodge F. A., Jr, Rahamimoff R. Co-operative action a calcium ions in transmitter release at the neuromuscular junction. J Physiol. 1967 Nov;193(2):419–432. doi: 10.1113/jphysiol.1967.sp008367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Haydon P. G., Henderson E., Stanley E. F. Localization of individual calcium channels at the release face of a presynaptic nerve terminal. Neuron. 1994 Dec;13(6):1275–1280. doi: 10.1016/0896-6273(94)90414-6. [DOI] [PubMed] [Google Scholar]
  19. Helmchen F., Borst J. G., Sakmann B. Calcium dynamics associated with a single action potential in a CNS presynaptic terminal. Biophys J. 1997 Mar;72(3):1458–1471. doi: 10.1016/S0006-3495(97)78792-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Heuser J. E., Reese T. S., Landis D. M. Functional changes in frog neuromuscular junctions studied with freeze-fracture. J Neurocytol. 1974 Mar;3(1):109–131. doi: 10.1007/BF01111936. [DOI] [PubMed] [Google Scholar]
  21. Katz E., Ferro P. A., Cherksey B. D., Sugimori M., Llinás R., Uchitel O. D. Effects of Ca2+ channel blockers on transmitter release and presynaptic currents at the frog neuromuscular junction. J Physiol. 1995 Aug 1;486(Pt 3):695–706. doi: 10.1113/jphysiol.1995.sp020845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Llinás R., Sugimori M., Simon S. M. Transmission by presynaptic spike-like depolarization in the squid giant synapse. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2415–2419. doi: 10.1073/pnas.79.7.2415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Luebke J. I., Dunlap K., Turner T. J. Multiple calcium channel types control glutamatergic synaptic transmission in the hippocampus. Neuron. 1993 Nov;11(5):895–902. doi: 10.1016/0896-6273(93)90119-c. [DOI] [PubMed] [Google Scholar]
  24. Mintz I. M., Sabatini B. L., Regehr W. G. Calcium control of transmitter release at a cerebellar synapse. Neuron. 1995 Sep;15(3):675–688. doi: 10.1016/0896-6273(95)90155-8. [DOI] [PubMed] [Google Scholar]
  25. Neher E. The use of fura-2 for estimating Ca buffers and Ca fluxes. Neuropharmacology. 1995 Nov;34(11):1423–1442. doi: 10.1016/0028-3908(95)00144-u. [DOI] [PubMed] [Google Scholar]
  26. Neher E. Vesicle pools and Ca2+ microdomains: new tools for understanding their roles in neurotransmitter release. Neuron. 1998 Mar;20(3):389–399. doi: 10.1016/s0896-6273(00)80983-6. [DOI] [PubMed] [Google Scholar]
  27. Oertel D. Encoding of timing in the brain stem auditory nuclei of vertebrates. Neuron. 1997 Nov;19(5):959–962. doi: 10.1016/s0896-6273(00)80388-8. [DOI] [PubMed] [Google Scholar]
  28. Ohana O., Sakmann B. Transmitter release modulation in nerve terminals of rat neocortical pyramidal cells by intracellular calcium buffers. J Physiol. 1998 Nov 15;513(Pt 1):135–148. doi: 10.1111/j.1469-7793.1998.135by.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Olivera B. M., Cruz L. J., de Santos V., LeCheminant G. W., Griffin D., Zeikus R., McIntosh J. M., Galyean R., Varga J., Gray W. R. Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom. Biochemistry. 1987 Apr 21;26(8):2086–2090. doi: 10.1021/bi00382a004. [DOI] [PubMed] [Google Scholar]
  30. Pape P. C., Jong D. S., Chandler W. K. Calcium release and its voltage dependence in frog cut muscle fibers equilibrated with 20 mM EGTA. J Gen Physiol. 1995 Aug;106(2):259–336. doi: 10.1085/jgp.106.2.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pumplin D. W., Reese T. S., Llinás R. Are the presynaptic membrane particles the calcium channels? Proc Natl Acad Sci U S A. 1981 Nov;78(11):7210–7213. doi: 10.1073/pnas.78.11.7210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Roberts W. M., Jacobs R. A., Hudspeth A. J. Colocalization of ion channels involved in frequency selectivity and synaptic transmission at presynaptic active zones of hair cells. J Neurosci. 1990 Nov;10(11):3664–3684. doi: 10.1523/JNEUROSCI.10-11-03664.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Robitaille R., Adler E. M., Charlton M. P. Strategic location of calcium channels at transmitter release sites of frog neuromuscular synapses. Neuron. 1990 Dec;5(6):773–779. doi: 10.1016/0896-6273(90)90336-e. [DOI] [PubMed] [Google Scholar]
  34. Robitaille R., Garcia M. L., Kaczorowski G. J., Charlton M. P. Functional colocalization of calcium and calcium-gated potassium channels in control of transmitter release. Neuron. 1993 Oct;11(4):645–655. doi: 10.1016/0896-6273(93)90076-4. [DOI] [PubMed] [Google Scholar]
  35. Sabatini B. L., Regehr W. G. Control of neurotransmitter release by presynaptic waveform at the granule cell to Purkinje cell synapse. J Neurosci. 1997 May 15;17(10):3425–3435. doi: 10.1523/JNEUROSCI.17-10-03425.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schweizer F. E., Betz H., Augustine G. J. From vesicle docking to endocytosis: intermediate reactions of exocytosis. Neuron. 1995 Apr;14(4):689–696. doi: 10.1016/0896-6273(95)90213-9. [DOI] [PubMed] [Google Scholar]
  37. Spencer A. N., Przysiezniak J., Acosta-Urquidi J., Basarsky T. A. Presynaptic spike broadening reduces junctional potential amplitude. Nature. 1989 Aug 24;340(6235):636–638. doi: 10.1038/340636a0. [DOI] [PubMed] [Google Scholar]
  38. Stanley E. F., Mirotznik R. R. Cleavage of syntaxin prevents G-protein regulation of presynaptic calcium channels. Nature. 1997 Jan 23;385(6614):340–343. doi: 10.1038/385340a0. [DOI] [PubMed] [Google Scholar]
  39. Stanley E. F. Single calcium channels and acetylcholine release at a presynaptic nerve terminal. Neuron. 1993 Dec;11(6):1007–1011. doi: 10.1016/0896-6273(93)90214-c. [DOI] [PubMed] [Google Scholar]
  40. Stanley E. F. Single calcium channels on a cholinergic presynaptic nerve terminal. Neuron. 1991 Oct;7(4):585–591. doi: 10.1016/0896-6273(91)90371-6. [DOI] [PubMed] [Google Scholar]
  41. Takahashi T., Forsythe I. D., Tsujimoto T., Barnes-Davies M., Onodera K. Presynaptic calcium current modulation by a metabotropic glutamate receptor. Science. 1996 Oct 25;274(5287):594–597. doi: 10.1126/science.274.5287.594. [DOI] [PubMed] [Google Scholar]
  42. Takahashi T., Momiyama A. Different types of calcium channels mediate central synaptic transmission. Nature. 1993 Nov 11;366(6451):156–158. doi: 10.1038/366156a0. [DOI] [PubMed] [Google Scholar]
  43. Wiser O., Bennett M. K., Atlas D. Functional interaction of syntaxin and SNAP-25 with voltage-sensitive L- and N-type Ca2+ channels. EMBO J. 1996 Aug 15;15(16):4100–4110. [PMC free article] [PubMed] [Google Scholar]
  44. Wu L. G., Borst J. G., Sakmann B. R-type Ca2+ currents evoke transmitter release at a rat central synapse. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4720–4725. doi: 10.1073/pnas.95.8.4720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wu L. G., Saggau P. Pharmacological identification of two types of presynaptic voltage-dependent calcium channels at CA3-CA1 synapses of the hippocampus. J Neurosci. 1994 Sep;14(9):5613–5622. doi: 10.1523/JNEUROSCI.14-09-05613.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wu L. G., Saggau P. Presynaptic inhibition of elicited neurotransmitter release. Trends Neurosci. 1997 May;20(5):204–212. doi: 10.1016/s0166-2236(96)01015-6. [DOI] [PubMed] [Google Scholar]
  47. Wu L. G., Westenbroek R. E., Borst J. G., Catterall W. A., Sakmann B. Calcium channel types with distinct presynaptic localization couple differentially to transmitter release in single calyx-type synapses. J Neurosci. 1999 Jan 15;19(2):726–736. doi: 10.1523/JNEUROSCI.19-02-00726.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Yamada W. M., Zucker R. S. Time course of transmitter release calculated from simulations of a calcium diffusion model. Biophys J. 1992 Mar;61(3):671–682. doi: 10.1016/S0006-3495(92)81872-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Yawo H., Momiyama A. Re-evaluation of calcium currents in pre- and postsynaptic neurones of the chick ciliary ganglion. J Physiol. 1993 Jan;460:153–172. doi: 10.1113/jphysiol.1993.sp019464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Yoshikami D., Bagabaldo Z., Olivera B. M. The inhibitory effects of omega-conotoxins on Ca channels and synapses. Ann N Y Acad Sci. 1989;560:230–248. doi: 10.1111/j.1749-6632.1989.tb24100.x. [DOI] [PubMed] [Google Scholar]
  51. Zengel J. E., Sosa M. A., Poage R. E. omega-Conotoxin reduces facilitation of transmitter release at the frog neuromuscular junction. Brain Res. 1993 May 14;611(1):25–30. doi: 10.1016/0006-8993(93)91772-k. [DOI] [PubMed] [Google Scholar]
  52. Zhang Z. W., Coggan J. S., Berg D. K. Synaptic currents generated by neuronal acetylcholine receptors sensitive to alpha-bungarotoxin. Neuron. 1996 Dec;17(6):1231–1240. doi: 10.1016/s0896-6273(00)80253-6. [DOI] [PubMed] [Google Scholar]
  53. Zucker R. S., Delaney K. R., Mulkey R., Tank D. W. Presynaptic calcium in transmitter release and posttetanic potentiation. Ann N Y Acad Sci. 1991;635:191–207. doi: 10.1111/j.1749-6632.1991.tb36492.x. [DOI] [PubMed] [Google Scholar]
  54. Zucker R. S. Exocytosis: a molecular and physiological perspective. Neuron. 1996 Dec;17(6):1049–1055. doi: 10.1016/s0896-6273(00)80238-x. [DOI] [PubMed] [Google Scholar]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

RESOURCES