Skip to main content
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
. 1993 Oct 15;90(20):9388–9392. doi: 10.1073/pnas.90.20.9388

Residual free calcium is not responsible for facilitation of neurotransmitter release.

J A Blundon 1, S N Wright 1, M S Brodwick 1, G D Bittner 1
PMCID: PMC47573  PMID: 8105475

Abstract

An increase in internal free calcium ([Ca2+]i) in the presynaptic terminal is often assumed to directly produce facilitation of neurotransmitter release. Using a Ca(2+)-activated potassium conductance as a bioassay for free [Ca2+]i in the presynaptic terminal of the crayfish (Procambarus clarkii) opener neuromuscular junction, we now demonstrate that free [Ca2+]i has a decay time constant (tau) of 1-4 msec, whereas facilitation of neurotransmitter release has a decay tau of 7-43 msec. In addition, facilitation of neurotransmitter release can be markedly different at times when free [Ca2+]i values and presynaptic membrane voltages are equal. We conclude that free [Ca2+]i in the presynaptic terminal is not directly responsible for facilitation of neurotransmitter release. Our data suggest that facilitation results from bound Ca2+ or some long-lived consequence of bound Ca2+.

Full text

PDF
9388

Selected References

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

  1. Bain A. I., Quastel D. M. Multiplicative and additive Ca(2+)-dependent components of facilitation at mouse endplates. J Physiol. 1992 Sep;455:383–405. doi: 10.1113/jphysiol.1992.sp019307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balnave R. J., Gage P. W. On facilitation of transmitter release at the toad neuromuscular junction. J Physiol. 1974 Jun;239(3):657–675. doi: 10.1113/jphysiol.1974.sp010588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bittner G. D., Schatz R. A. An examination of the residual calcium theory for facilitation of transmitter release. Brain Res. 1981 Apr 6;210(1-2):431–436. doi: 10.1016/0006-8993(81)90922-7. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Fogelson A. L., Zucker R. S. Presynaptic calcium diffusion from various arrays of single channels. Implications for transmitter release and synaptic facilitation. Biophys J. 1985 Dec;48(6):1003–1017. doi: 10.1016/S0006-3495(85)83863-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. HODGKIN A. L., HUXLEY A. F. The components of membrane conductance in the giant axon of Loligo. J Physiol. 1952 Apr;116(4):473–496. doi: 10.1113/jphysiol.1952.sp004718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Katz B., Miledi R. The role of calcium in neuromuscular facilitation. J Physiol. 1968 Mar;195(2):481–492. doi: 10.1113/jphysiol.1968.sp008469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Latorre R., Oberhauser A., Labarca P., Alvarez O. Varieties of calcium-activated potassium channels. Annu Rev Physiol. 1989;51:385–399. doi: 10.1146/annurev.ph.51.030189.002125. [DOI] [PubMed] [Google Scholar]
  9. Llinás R., Gruner J. A., Sugimori M., McGuinness T. L., Greengard P. Regulation by synapsin I and Ca(2+)-calmodulin-dependent protein kinase II of the transmitter release in squid giant synapse. J Physiol. 1991 May;436:257–282. doi: 10.1113/jphysiol.1991.sp018549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Llinás R., McGuinness T. L., Leonard C. S., Sugimori M., Greengard P. Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse. Proc Natl Acad Sci U S A. 1985 May;82(9):3035–3039. doi: 10.1073/pnas.82.9.3035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Llinás R., Sugimori M., Silver R. B. Microdomains of high calcium concentration in a presynaptic terminal. Science. 1992 May 1;256(5057):677–679. doi: 10.1126/science.1350109. [DOI] [PubMed] [Google Scholar]
  13. Mallart A., Martin A. R. An analysis of facilitation of transmitter release at the neuromuscular junction of the frog. J Physiol. 1967 Dec;193(3):679–694. doi: 10.1113/jphysiol.1967.sp008388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Robitaille R., Charlton M. P. Frequency facilitation is not caused by residual ionized calcium at the frog neuromuscular junction. Ann N Y Acad Sci. 1991;635:492–494. doi: 10.1111/j.1749-6632.1991.tb36537.x. [DOI] [PubMed] [Google Scholar]
  17. Robitaille R., Charlton M. P. Presynaptic calcium signals and transmitter release are modulated by calcium-activated potassium channels. J Neurosci. 1992 Jan;12(1):297–305. doi: 10.1523/JNEUROSCI.12-01-00297.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Silinsky E. M. The biophysical pharmacology of calcium-dependent acetylcholine secretion. Pharmacol Rev. 1985 Mar;37(1):81–132. [PubMed] [Google Scholar]
  19. Sivaramakrishnan S., Bittner G. D., Brodwick M. S. Calcium-activated potassium conductance in presynaptic terminals at the crayfish neuromuscular junction. J Gen Physiol. 1991 Dec;98(6):1161–1179. doi: 10.1085/jgp.98.6.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sivaramakrishnan S., Brodwick M. S., Bittner G. D. Presynaptic facilitation at the crayfish neuromuscular junction. Role of calcium-activated potassium conductance. J Gen Physiol. 1991 Dec;98(6):1181–1196. doi: 10.1085/jgp.98.6.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stanley E. F. Decline in calcium cooperativity as the basis of facilitation at the squid giant synapse. J Neurosci. 1986 Mar;6(3):782–789. doi: 10.1523/JNEUROSCI.06-03-00782.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Swandulla D., Hans M., Zipser K., Augustine G. J. Role of residual calcium in synaptic depression and posttetanic potentiation: fast and slow calcium signaling in nerve terminals. Neuron. 1991 Dec;7(6):915–926. doi: 10.1016/0896-6273(91)90337-y. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Zucker R. S., Stockbridge N. Presynaptic calcium diffusion and the time courses of transmitter release and synaptic facilitation at the squid giant synapse. J Neurosci. 1983 Jun;3(6):1263–1269. doi: 10.1523/JNEUROSCI.03-06-01263.1983. [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