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. 1995 Jul 15;486(Pt 2):411–426. doi: 10.1113/jphysiol.1995.sp020822

Burst kinetics of single NMDA receptor currents in cell-attached patches from rat brain cortical neurons in culture.

N W Kleckner 1, B S Pallotta 1
PMCID: PMC1156531  PMID: 7473207

Abstract

1. The patch-clamp technique was used to record single-channel currents from cell-attached patches on rat brain cortical neurons in culture. The composition of the open and shut intervals during bursts of openings was studied in N-methyl-D-aspartate (NMDA) receptors exposed to 1 microM NMDA and 10 microM glycine at a membrane potential of -70 mV. 2. Open interval histograms were constructed for openings at each position (first, second, third, etc.) during all bursts. Distributions from openings two to five were fitted with similar (two or three) exponential components. The first opening from all bursts tended to be of shorter duration than the other openings. 3. Bursts were sorted according to the number of openings they contained and duration histograms were obtained for the openings at each position (one to five) during bursts of up to five openings. For bursts containing two or more openings, the distribution of open durations obtained at a given position were similar to each other regardless of the number of openings in the burst. 4. In bursts of two or more openings (up to five), duration histograms from the openings at each position in the burst were fitted with two or three exponential components that were similar for each opening. Bursts consisting of a single opening had a different distribution, having a relatively larger component of short duration. 5. Shut intervals during bursts were described by two exponential components with average time constants (and relative areas) (means +/- S.E.M.) of 0.06 +/- 0.01 ms (0.59 +/- 0.02) and 0.64 +/- 0.02 ms (0.41 +/- 0.02). Their distribution was independent of the numbers of openings in the bursts, their position within the burst, and the types of openings (long or short duration) contained within the burst. 6. These results suggest that each opening in bursts of two or more openings is kinetically similar to every other opening regardless of burst length. Analogously, each shut period during a burst was similar to every other. A kinetic model with three open and four closed intraburst states is shown to be consistent with these results for bursts of two or more openings.

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Selected References

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

  1. Ascher P., Nowak L. The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture. J Physiol. 1988 May;399:247–266. doi: 10.1113/jphysiol.1988.sp017078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beal M. F. Mechanisms of excitotoxicity in neurologic diseases. FASEB J. 1992 Dec;6(15):3338–3344. [PubMed] [Google Scholar]
  3. Benveniste M., Clements J., Vyklický L., Jr, Mayer M. L. A kinetic analysis of the modulation of N-methyl-D-aspartic acid receptors by glycine in mouse cultured hippocampal neurones. J Physiol. 1990 Sep;428:333–357. doi: 10.1113/jphysiol.1990.sp018215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benveniste M., Mayer M. L. Kinetic analysis of antagonist action at N-methyl-D-aspartic acid receptors. Two binding sites each for glutamate and glycine. Biophys J. 1991 Mar;59(3):560–573. doi: 10.1016/S0006-3495(91)82272-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blatz A. L., Magleby K. L. Adjacent interval analysis distinguishes among gating mechanisms for the fast chloride channel from rat skeletal muscle. J Physiol. 1989 Mar;410:561–585. doi: 10.1113/jphysiol.1989.sp017549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clements J. D., Lester R. A., Tong G., Jahr C. E., Westbrook G. L. The time course of glutamate in the synaptic cleft. Science. 1992 Nov 27;258(5087):1498–1501. doi: 10.1126/science.1359647. [DOI] [PubMed] [Google Scholar]
  7. Clements J. D., Westbrook G. L. Activation kinetics reveal the number of glutamate and glycine binding sites on the N-methyl-D-aspartate receptor. Neuron. 1991 Oct;7(4):605–613. doi: 10.1016/0896-6273(91)90373-8. [DOI] [PubMed] [Google Scholar]
  8. Colquhoun D., Hawkes A. G. A note on correlations in single ion channel records. Proc R Soc Lond B Biol Sci. 1987 Feb 23;230(1258):15–52. doi: 10.1098/rspb.1987.0008. [DOI] [PubMed] [Google Scholar]
  9. Colquhoun D., Hawkes A. G. On the stochastic properties of bursts of single ion channel openings and of clusters of bursts. Philos Trans R Soc Lond B Biol Sci. 1982 Dec 24;300(1098):1–59. doi: 10.1098/rstb.1982.0156. [DOI] [PubMed] [Google Scholar]
  10. Colquhoun D., Hawkes A. G. On the stochastic properties of single ion channels. Proc R Soc Lond B Biol Sci. 1981 Mar 6;211(1183):205–235. doi: 10.1098/rspb.1981.0003. [DOI] [PubMed] [Google Scholar]
  11. Colquhoun D., Hawkes A. G. Stochastic properties of ion channel openings and bursts in a membrane patch that contains two channels: evidence concerning the number of channels present when a record containing only single openings is observed. Proc R Soc Lond B Biol Sci. 1990 Jun 22;240(1299):453–477. doi: 10.1098/rspb.1990.0048. [DOI] [PubMed] [Google Scholar]
  12. Colquhoun D., Sakmann B. Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate. J Physiol. 1985 Dec;369:501–557. doi: 10.1113/jphysiol.1985.sp015912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Colquhoun D., Sakmann B. Fluctuations in the microsecond time range of the current through single acetylcholine receptor ion channels. Nature. 1981 Dec 3;294(5840):464–466. doi: 10.1038/294464a0. [DOI] [PubMed] [Google Scholar]
  14. Cull-Candy S. G., Usowicz M. M. Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nature. 1987 Feb 5;325(6104):525–528. doi: 10.1038/325525a0. [DOI] [PubMed] [Google Scholar]
  15. Dionne V. E., Steinbach J. H., Stevens C. F. An analysis of the dose-response relationship at voltage-clamped frog neuromuscular junctions. J Physiol. 1978 Aug;281:421–444. doi: 10.1113/jphysiol.1978.sp012431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Donnelly J. L., Pallotta B. S. Single-channel currents from diethylpyrocarbonate-modified NMDA receptors in cultured rat brain cortical neurons. J Gen Physiol. 1995 Jun;105(6):837–859. doi: 10.1085/jgp.105.6.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Edmonds B., Colquhoun D. Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration. Proc Biol Sci. 1992 Dec 22;250(1329):279–286. doi: 10.1098/rspb.1992.0160. [DOI] [PubMed] [Google Scholar]
  18. Gibb A. J., Colquhoun D. Activation of N-methyl-D-aspartate receptors by L-glutamate in cells dissociated from adult rat hippocampus. J Physiol. 1992 Oct;456:143–179. doi: 10.1113/jphysiol.1992.sp019331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gibb A. J., Colquhoun D. Glutamate activation of a single NMDA receptor-channel produces a cluster of channel openings. Proc Biol Sci. 1991 Jan 22;243(1306):39–45. doi: 10.1098/rspb.1991.0007. [DOI] [PubMed] [Google Scholar]
  20. Hoch D. B., Dingledine R. GABAergic neurons in rat hippocampal culture. Brain Res. 1986 Feb;390(1):53–64. doi: 10.1016/0165-3806(86)90151-3. [DOI] [PubMed] [Google Scholar]
  21. Hollmann M., Heinemann S. Cloned glutamate receptors. Annu Rev Neurosci. 1994;17:31–108. doi: 10.1146/annurev.ne.17.030194.000335. [DOI] [PubMed] [Google Scholar]
  22. Horn R. Statistical methods for model discrimination. Applications to gating kinetics and permeation of the acetylcholine receptor channel. Biophys J. 1987 Feb;51(2):255–263. doi: 10.1016/S0006-3495(87)83331-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Howe J. R., Cull-Candy S. G., Colquhoun D. Currents through single glutamate receptor channels in outside-out patches from rat cerebellar granule cells. J Physiol. 1991 Jan;432:143–202. doi: 10.1113/jphysiol.1991.sp018381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jahr C. E., Stevens C. F. A quantitative description of NMDA receptor-channel kinetic behavior. J Neurosci. 1990 Jun;10(6):1830–1837. doi: 10.1523/JNEUROSCI.10-06-01830.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jahr C. E., Stevens C. F. Glutamate activates multiple single channel conductances in hippocampal neurons. Nature. 1987 Feb 5;325(6104):522–525. doi: 10.1038/325522a0. [DOI] [PubMed] [Google Scholar]
  26. Kerry C. J., Kits K. S., Ramsey R. L., Sansom M. S., Usherwood P. N. Single channel kinetics of a glutamate receptor. Biophys J. 1987 Jan;51(1):137–144. doi: 10.1016/S0006-3495(87)83318-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Korn S. J., Horn R. Statistical discrimination of fractal and Markov models of single-channel gating. Biophys J. 1988 Nov;54(5):871–877. doi: 10.1016/S0006-3495(88)83023-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Krishtal O. A., Pidoplichko V. I. A receptor for protons in the nerve cell membrane. Neuroscience. 1980;5(12):2325–2327. doi: 10.1016/0306-4522(80)90149-9. [DOI] [PubMed] [Google Scholar]
  29. Labarca P., Rice J. A., Fredkin D. R., Montal M. Kinetic analysis of channel gating. Application to the cholinergic receptor channel and the chloride channel from Torpedo californica. Biophys J. 1985 Apr;47(4):469–478. doi: 10.1016/S0006-3495(85)83939-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lester R. A., Clements J. D., Westbrook G. L., Jahr C. E. Channel kinetics determine the time course of NMDA receptor-mediated synaptic currents. Nature. 1990 Aug 9;346(6284):565–567. doi: 10.1038/346565a0. [DOI] [PubMed] [Google Scholar]
  31. Lester R. A., Tong G., Jahr C. E. Interactions between the glycine and glutamate binding sites of the NMDA receptor. J Neurosci. 1993 Mar;13(3):1088–1096. doi: 10.1523/JNEUROSCI.13-03-01088.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lin F., Stevens C. F. Both open and closed NMDA receptor channels desensitize. J Neurosci. 1994 Apr;14(4):2153–2160. doi: 10.1523/JNEUROSCI.14-04-02153.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Macdonald R. L., Rogers C. J., Twyman R. E. Kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurones in culture. J Physiol. 1989 Mar;410:479–499. doi: 10.1113/jphysiol.1989.sp017545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Magleby K. L. Ion channels. Preventing artifacts and reducing errors in single-channel analysis. Methods Enzymol. 1992;207:763–791. doi: 10.1016/0076-6879(92)07055-s. [DOI] [PubMed] [Google Scholar]
  35. Magleby K. L., Pallotta B. S. Burst kinetics of single calcium-activated potassium channels in cultured rat muscle. J Physiol. 1983 Nov;344:605–623. doi: 10.1113/jphysiol.1983.sp014958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Magleby K. L., Pallotta B. S. Calcium dependence of open and shut interval distributions from calcium-activated potassium channels in cultured rat muscle. J Physiol. 1983 Nov;344:585–604. doi: 10.1113/jphysiol.1983.sp014957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. McBain C. J., Mayer M. L. N-methyl-D-aspartic acid receptor structure and function. Physiol Rev. 1994 Jul;74(3):723–760. doi: 10.1152/physrev.1994.74.3.723. [DOI] [PubMed] [Google Scholar]
  38. McManus O. B., Magleby K. L. Kinetic states and modes of single large-conductance calcium-activated potassium channels in cultured rat skeletal muscle. J Physiol. 1988 Aug;402:79–120. doi: 10.1113/jphysiol.1988.sp017195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2;307(5950):462–465. doi: 10.1038/307462a0. [DOI] [PubMed] [Google Scholar]
  40. Sather W., Dieudonné S., MacDonald J. F., Ascher P. Activation and desensitization of N-methyl-D-aspartate receptors in nucleated outside-out patches from mouse neurones. J Physiol. 1992 May;450:643–672. doi: 10.1113/jphysiol.1992.sp019148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sigworth F. J., Sine S. M. Data transformations for improved display and fitting of single-channel dwell time histograms. Biophys J. 1987 Dec;52(6):1047–1054. doi: 10.1016/S0006-3495(87)83298-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Twyman R. E., Rogers C. J., Macdonald R. L. Intraburst kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurones in culture. J Physiol. 1990 Apr;423:193–220. doi: 10.1113/jphysiol.1990.sp018018. [DOI] [PMC free article] [PubMed] [Google Scholar]

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