Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 May 24;91(11):4771–4775. doi: 10.1073/pnas.91.11.4771

N- and P-type Ca2+ channels are involved in acetylcholine release at a neuroneuronal synapse: only the N-type channel is the target of neuromodulators.

P Fossier 1, G Baux 1, L Tauc 1
PMCID: PMC43870  PMID: 7910963

Abstract

Cholinergic transmission in an identified neuro-neuronal synapse of the Aplysia buccal ganglion was depressed by application of a partially purified extract of the funnel-web-spider venom (FTx) or of its synthetic analog (sFTx). This specific blocker of voltage-dependent P-type Ca2+ channels did not interfere with the effect of the N-type Ca2+ channel blocker omega-conotoxin, which could further decrease synaptic transmission after a previous application of FTx. Similar results were obtained when the reversal order of application of these two Ca2+ channel blockers was used. Both P- and N-type Ca2+ currents trigger acetylcholine release in the presynaptic neuron. The neuromodulatory effects of FMRF-amide, histamine, and buccalin on transmitter release disappeared after the blockade of the N-type Ca2+ channels but remained still effective in the presence of FTx. These results indicate that only N-type Ca2+ channels appear to be sensitive to the neuromodulators we have identified.

Full text

PDF
4772

Selected References

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

  1. Altiere R. J., Diamond L., Thompson D. C. Omega-conotoxin-sensitive calcium channels modulate autonomic neurotransmission in guinea pig airways. J Pharmacol Exp Ther. 1992 Jan;260(1):98–103. [PubMed] [Google Scholar]
  2. Baux G., Fossier P., Tauc L. Histamine and FLRFamide regulate acetylcholine release at an identified synapse in Aplysia in opposite ways. J Physiol. 1990 Oct;429:147–168. doi: 10.1113/jphysiol.1990.sp018249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baux G., Fossier P., Trudeau L. E., Tauc L. Transmitter release and calcium currents at an Aplysia buccal ganglion synapse--II. Modulation by presynaptic receptors. Neuroscience. 1993 Mar;53(2):581–593. doi: 10.1016/0306-4522(93)90223-3. [DOI] [PubMed] [Google Scholar]
  4. Baux G., Tauc L. Presynaptic actions of curare and atropine on quantal acetylcholine release at a central synapse of Aplysia. J Physiol. 1987 Jul;388:665–680. doi: 10.1113/jphysiol.1987.sp016637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cahill C. M., White T. D., Sawynok J. Involvement of calcium channels in depolarization-evoked release of adenosine from spinal cord synaptosomes. J Neurochem. 1993 Mar;60(3):886–893. doi: 10.1111/j.1471-4159.1993.tb03233.x. [DOI] [PubMed] [Google Scholar]
  6. Ceña V., Nicolas G. P., Sanchez-Garcia P., Kirpekar S. M., Garcia A. G. Pharmacological dissection of receptor-associated and voltage-sensitive ionic channels involved in catecholamine release. Neuroscience. 1983 Dec;10(4):1455–1462. doi: 10.1016/0306-4522(83)90126-4. [DOI] [PubMed] [Google Scholar]
  7. Chad J., Eckert R., Ewald D. Kinetics of calcium-dependent inactivation of calcium current in voltage-clamped neurones of Aplysia californica. J Physiol. 1984 Feb;347:279–300. doi: 10.1113/jphysiol.1984.sp015066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cherksey B. D., Sugimori M., Llinás R. R. Properties of calcium channels isolated with spider toxin, FTX. Ann N Y Acad Sci. 1991;635:80–89. doi: 10.1111/j.1749-6632.1991.tb36483.x. [DOI] [PubMed] [Google Scholar]
  9. Church P. J., Lloyd P. E. Expression of diverse neuropeptide cotransmitters by identified motor neurons in Aplysia. J Neurosci. 1991 Mar;11(3):618–625. doi: 10.1523/JNEUROSCI.11-03-00618.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clasbrummel B., Osswald H., Illes P. Inhibition of noradrenaline release by omega-conotoxin GVIA in the rat tail artery. Br J Pharmacol. 1989 Jan;96(1):101–110. doi: 10.1111/j.1476-5381.1989.tb11789.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. De Luca A., Li C. G., Rand M. J., Reid J. J., Thaina P., Wong-Dusting H. K. Effects of omega-conotoxin GVIA on autonomic neuroeffector transmission in various tissues. Br J Pharmacol. 1990 Oct;101(2):437–447. doi: 10.1111/j.1476-5381.1990.tb12727.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. De Luca A., Rand M. J., Reid J. J., Story D. F. Differential sensitivities of avian and mammalian neuromuscular junctions to inhibition of cholinergic transmission by omega-conotoxin GVIA. Toxicon. 1991;29(3):311–320. doi: 10.1016/0041-0101(91)90284-x. [DOI] [PubMed] [Google Scholar]
  13. Dooley D. J., Lupp A., Hertting G. Inhibition of central neurotransmitter release by omega-conotoxin GVIA, a peptide modulator of the N-type voltage-sensitive calcium channel. Naunyn Schmiedebergs Arch Pharmacol. 1987 Oct;336(4):467–470. doi: 10.1007/BF00164885. [DOI] [PubMed] [Google Scholar]
  14. Dooley D. J., Lupp A., Hertting G., Osswald H. Omega-conotoxin GVIA and pharmacological modulation of hippocampal noradrenaline release. Eur J Pharmacol. 1988 Mar 29;148(2):261–267. doi: 10.1016/0014-2999(88)90572-9. [DOI] [PubMed] [Google Scholar]
  15. Edmonds B., Klein M., Dale N., Kandel E. R. Contributions of two types of calcium channels to synaptic transmission and plasticity. Science. 1990 Nov 23;250(4984):1142–1147. doi: 10.1126/science.2174573. [DOI] [PubMed] [Google Scholar]
  16. Elmslie K. S., Kammermeier P. J., Jones S. W. Calcium current modulation in frog sympathetic neurones: L-current is relatively insensitive to neurotransmitters. J Physiol. 1992 Oct;456:107–123. doi: 10.1113/jphysiol.1992.sp019329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Feuerstein T. J., Dooley D. J., Seeger W. Inhibition of norepinephrine and acetylcholine release from human neocortex by omega-conotoxin GVIA. J Pharmacol Exp Ther. 1990 Feb;252(2):778–785. [PubMed] [Google Scholar]
  18. Fossier P., Baux G., Tauc L. Activation of protein kinase C by presynaptic FLRFamide receptors facilitates transmitter release at an aplysia cholinergic synapse. Neuron. 1990 Oct;5(4):479–486. doi: 10.1016/0896-6273(90)90087-v. [DOI] [PubMed] [Google Scholar]
  19. Fossier P., Baux G., Trudeau L. E., Tauc L. Involvement of Ca2+ uptake by a reticulum-like store in the control of transmitter release. Neuroscience. 1992 Sep;50(2):427–434. doi: 10.1016/0306-4522(92)90434-4. [DOI] [PubMed] [Google Scholar]
  20. Fossier P., Baux G., Trudeau L. E., Tauc L. Pre- and postsynaptic actions of nifedipine at an identified cholinergic central synapse of Aplysia. Pflugers Arch. 1992 Nov;422(2):193–197. doi: 10.1007/BF00370420. [DOI] [PubMed] [Google Scholar]
  21. Hermann A., Gorman A. L. Effects of 4-aminopyridine on potassium currents in a molluscan neuron. J Gen Physiol. 1981 Jul;78(1):63–86. doi: 10.1085/jgp.78.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hirning L. D., Fox A. P., McCleskey E. W., Olivera B. M., Thayer S. A., Miller R. J., Tsien R. W. Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons. Science. 1988 Jan 1;239(4835):57–61. doi: 10.1126/science.2447647. [DOI] [PubMed] [Google Scholar]
  23. Horne A. L., Kemp J. A. The effect of omega-conotoxin GVIA on synaptic transmission within the nucleus accumbens and hippocampus of the rat in vitro. Br J Pharmacol. 1991 Jul;103(3):1733–1739. doi: 10.1111/j.1476-5381.1991.tb09855.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kasai H., Neher E. Dihydropyridine-sensitive and omega-conotoxin-sensitive calcium channels in a mammalian neuroblastoma-glioma cell line. J Physiol. 1992 Mar;448:161–188. doi: 10.1113/jphysiol.1992.sp019035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Keith R. A., Mangano T. J., Pacheco M. A., Salama A. I. Characterization of the effects of omega-conotoxin GVIA on the responses of voltage-sensitive calcium channels. J Auton Pharmacol. 1989 Aug;9(4):243–252. doi: 10.1111/j.1474-8673.1989.tb00215.x. [DOI] [PubMed] [Google Scholar]
  26. Llinás R., Sugimori M., Hillman D. E., Cherksey B. Distribution and functional significance of the P-type, voltage-dependent Ca2+ channels in the mammalian central nervous system. Trends Neurosci. 1992 Sep;15(9):351–355. doi: 10.1016/0166-2236(92)90053-b. [DOI] [PubMed] [Google Scholar]
  27. Llinás R., Sugimori M., Lin J. W., Cherksey B. Blocking and isolation of a calcium channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1689–1693. doi: 10.1073/pnas.86.5.1689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Llinás R., Sugimori M., Silver R. B. Presynaptic calcium concentration microdomains and transmitter release. J Physiol Paris. 1992;86(1-3):135–138. doi: 10.1016/s0928-4257(05)80018-x. [DOI] [PubMed] [Google Scholar]
  29. Lundy P. M., Frew R. Evidence of omega-conotoxin GV1A-sensitive Ca2+ channels in mammalian peripheral nerve terminals. Eur J Pharmacol. 1988 Nov 8;156(3):325–330. doi: 10.1016/0014-2999(88)90277-4. [DOI] [PubMed] [Google Scholar]
  30. Maggi C. A., Patacchini R., Giuliani S., Santicioli P., Meli A. Evidence for two independent modes of activation of the 'efferent' function of capsaicin-sensitive nerves. Eur J Pharmacol. 1988 Nov 8;156(3):367–373. doi: 10.1016/0014-2999(88)90282-8. [DOI] [PubMed] [Google Scholar]
  31. Maggi C. A., Patacchini R., Santicioli P., Lippe I. T., Giuliani S., Geppetti P., Del Bianco E., Selleri S., Meli A. The effect of omega conotoxin GVIA, a peptide modulator of the N-type voltage sensitive calcium channels, on motor responses produced by activation of efferent and sensory nerves in mammalian smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1988 Aug;338(2):107–113. doi: 10.1007/BF00174856. [DOI] [PubMed] [Google Scholar]
  32. Maggi C. A., Tramontana M., Cecconi R., Santicioli P. Neurochemical evidence for the involvement of N-type calcium channels in transmitter secretion from peripheral endings of sensory nerves in guinea pigs. Neurosci Lett. 1990 Jul 3;114(2):203–206. doi: 10.1016/0304-3940(90)90072-h. [DOI] [PubMed] [Google Scholar]
  33. Moulian N., Gaudry-Talarmain Y. M. Agelenopsis aperta venom and FTX, a purified toxin, inhibit acetylcholine release in Torpedo synaptosomes. Neuroscience. 1993 Jun;54(4):1035–1041. doi: 10.1016/0306-4522(93)90593-5. [DOI] [PubMed] [Google Scholar]
  34. Perney T. M., Hirning L. D., Leeman S. E., Miller R. J. Multiple calcium channels mediate neurotransmitter release from peripheral neurons. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6656–6659. doi: 10.1073/pnas.83.17.6656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pin J. P., Bockaert J. Omega-conotoxin GVIA and dihydropyridines discriminate two types of Ca2+ channels involved in GABA release from striatal neurons in culture. Eur J Pharmacol. 1990 Jan 23;188(1):81–84. doi: 10.1016/0922-4106(90)90250-2. [DOI] [PubMed] [Google Scholar]
  36. Pruneau D., Angus J. A. Omega-conotoxin GVIA is a potent inhibitor of sympathetic neurogenic responses in rat small mesenteric arteries. Br J Pharmacol. 1990 May;100(1):180–184. doi: 10.1111/j.1476-5381.1990.tb12073.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Reynolds I. J., Wagner J. A., Snyder S. H., Thayer S. A., Olivera B. M., Miller R. J. Brain voltage-sensitive calcium channel subtypes differentiated by omega-conotoxin fraction GVIA. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8804–8807. doi: 10.1073/pnas.83.22.8804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Trudeau L. E., Baux G., Fossier P., Tauc L. Transmitter release and calcium currents at an Aplysia buccal ganglion synapse--I. Characterization. Neuroscience. 1993 Mar;53(2):571–580. doi: 10.1016/0306-4522(93)90222-2. [DOI] [PubMed] [Google Scholar]
  39. Turner T. J., Goldin S. M. Calcium channels in rat brain synaptosomes: identification and pharmacological characterization. High affinity blockade by organic Ca2+ channel blockers. J Neurosci. 1985 Mar;5(3):841–849. doi: 10.1523/JNEUROSCI.05-03-00841.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Uchitel O. D., Protti D. A., Sanchez V., Cherksey B. D., Sugimori M., Llinás R. P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3330–3333. doi: 10.1073/pnas.89.8.3330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wessler I., Dooley D. J., Werhand J., Schlemmer F. Differential effects of calcium channel antagonists (omega-conotoxin GVIA, nifedipine, verapamil) on the electrically-evoked release of [3H]acetylcholine from the myenteric plexus, phrenic nerve and neocortex of rats. Naunyn Schmiedebergs Arch Pharmacol. 1990 Apr;341(4):288–294. doi: 10.1007/BF00180653. [DOI] [PubMed] [Google Scholar]
  42. Zhang J. F., Randall A. D., Ellinor P. T., Horne W. A., Sather W. A., Tanabe T., Schwarz T. L., Tsien R. W. Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons. Neuropharmacology. 1993 Nov;32(11):1075–1088. doi: 10.1016/0028-3908(93)90003-l. [DOI] [PubMed] [Google Scholar]
  43. el-Din M. M., Malik K. U. Differential effect of omega-conotoxin on release of the adrenergic transmitter and the vasoconstrictor response to noradrenaline in the rat isolated kidney. Br J Pharmacol. 1988 Jun;94(2):355–362. doi: 10.1111/j.1476-5381.1988.tb11537.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES