Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1991;440:95–112. doi: 10.1113/jphysiol.1991.sp018698

The role of the beta 4-subunit in determining the kinetic properties of rat neuronal nicotinic acetylcholine alpha 3-receptors.

R L Papke 1, S F Heinemann 1
PMCID: PMC1180142  PMID: 1725184

Abstract

1. Single-channel currents were recorded from Xenopus oocytes which had been injected with complementary RNAs (cRNAs) for the neuronal nicotinic acetylcholine receptor subunits alpha 3 and beta 4. The co-expression of alpha 3 and beta 4 gave rise to three different channel types with conductances of 22, 18 and 13 pS. 2. The activity arising from the expression of these two subunits was compared with that observed when the alpha 3 subunit was co-expressed with an alternative beta-subunit, beta 2. The alpha 3 beta 4-receptors differed from alpha 3 beta 2-receptors in conductance, open times and most notably, in burst kinetics. The association of the beta 4-subunit with the alpha 3-subunit results in receptors which have a high probability of re-opening after closing, yielding protracted bursts of activity not observed when the alpha 3-subunit is associated with the beta 2-subunit. 3. All three alpha 3 beta 4-channel types had similar burst kinetics. However, the 13 pS conductance channels showed an additional long-lived open state to varying degrees when clusters of activity within an individual record were examined.

Full text

PDF
95

Images in this article

105Fig. 7
on p.105

Selected References

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

  1. Blount P., Merlie J. P. Molecular basis of the two nonequivalent ligand binding sites of the muscle nicotinic acetylcholine receptor. Neuron. 1989 Sep;3(3):349–357. doi: 10.1016/0896-6273(89)90259-6. [DOI] [PubMed] [Google Scholar]
  2. Bormann J., Matthaei H. Three types of acetylcholine-induced single channel currents in clonal rat pheochromocytoma cells. Neurosci Lett. 1983 Sep 30;40(2):193–197. doi: 10.1016/0304-3940(83)90301-4. [DOI] [PubMed] [Google Scholar]
  3. Boulter J., Connolly J., Deneris E., Goldman D., Heinemann S., Patrick J. Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7763–7767. doi: 10.1073/pnas.84.21.7763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boulter J., Evans K., Goldman D., Martin G., Treco D., Heinemann S., Patrick J. Isolation of a cDNA clone coding for a possible neural nicotinic acetylcholine receptor alpha-subunit. 1986 Jan 30-Feb 5Nature. 319(6052):368–374. doi: 10.1038/319368a0. [DOI] [PubMed] [Google Scholar]
  5. Clapham D. E., Neher E. Substance P reduces acetylcholine-induced currents in isolated bovine chromaffin cells. J Physiol. 1984 Feb;347:255–277. doi: 10.1113/jphysiol.1984.sp015065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Connolly J. G. Structure-function relationships in nicotinic acetylcholine receptors. Comp Biochem Physiol A Comp Physiol. 1989;93(1):221–231. doi: 10.1016/0300-9629(89)90210-7. [DOI] [PubMed] [Google Scholar]
  8. Couturier S., Bertrand D., Matter J. M., Hernandez M. C., Bertrand S., Millar N., Valera S., Barkas T., Ballivet M. A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX. Neuron. 1990 Dec;5(6):847–856. doi: 10.1016/0896-6273(90)90344-f. [DOI] [PubMed] [Google Scholar]
  9. Couturier S., Erkman L., Valera S., Rungger D., Bertrand S., Boulter J., Ballivet M., Bertrand D. Alpha 5, alpha 3, and non-alpha 3. Three clustered avian genes encoding neuronal nicotinic acetylcholine receptor-related subunits. J Biol Chem. 1990 Oct 15;265(29):17560–17567. [PubMed] [Google Scholar]
  10. Deneris E. S., Connolly J., Boulter J., Wada E., Wada K., Swanson L. W., Patrick J., Heinemann S. Primary structure and expression of beta 2: a novel subunit of neuronal nicotinic acetylcholine receptors. Neuron. 1988 Mar;1(1):45–54. doi: 10.1016/0896-6273(88)90208-5. [DOI] [PubMed] [Google Scholar]
  11. Duvoisin R. M., Deneris E. S., Patrick J., Heinemann S. The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit: beta 4. Neuron. 1989 Oct;3(4):487–496. doi: 10.1016/0896-6273(89)90207-9. [DOI] [PubMed] [Google Scholar]
  12. Fenwick E. M., Marty A., Neher E. A patch-clamp study of bovine chromaffin cells and of their sensitivity to acetylcholine. J Physiol. 1982 Oct;331:577–597. doi: 10.1113/jphysiol.1982.sp014393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldman D., Deneris E., Luyten W., Kochhar A., Patrick J., Heinemann S. Members of a nicotinic acetylcholine receptor gene family are expressed in different regions of the mammalian central nervous system. Cell. 1987 Mar 27;48(6):965–973. doi: 10.1016/0092-8674(87)90705-7. [DOI] [PubMed] [Google Scholar]
  14. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  15. Jaramillo F., Schuetze S. M. Kinetic differences between embryonic- and adult-type acetylcholine receptors in rat myotubes. J Physiol. 1988 Feb;396:267–296. doi: 10.1113/jphysiol.1988.sp016962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Labarca P., Montal M. S., Lindstrom J. M., Montal M. The occurrence of long openings in the purified cholinergic receptor channel increases with acetylcholine concentration. J Neurosci. 1985 Dec;5(12):3409–3413. doi: 10.1523/JNEUROSCI.05-12-03409.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lo D. C., Pinkham J. L., Stevens C. F. Influence of the gamma subunit and expression system on acetylcholine receptor gating. Neuron. 1990 Dec;5(6):857–866. doi: 10.1016/0896-6273(90)90345-g. [DOI] [PubMed] [Google Scholar]
  18. Luetje C. W., Patrick J. Both alpha- and beta-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors. J Neurosci. 1991 Mar;11(3):837–845. doi: 10.1523/JNEUROSCI.11-03-00837.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Moss B. L., Schuetze S. M., Role L. W. Functional properties and developmental regulation of nicotinic acetylcholine receptors on embryonic chicken sympathetic neurons. Neuron. 1989 Nov;3(5):597–607. doi: 10.1016/0896-6273(89)90270-5. [DOI] [PubMed] [Google Scholar]
  20. Papke R. L., Boulter J., Patrick J., Heinemann S. Single-channel currents of rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. Neuron. 1989 Nov;3(5):589–596. doi: 10.1016/0896-6273(89)90269-9. [DOI] [PubMed] [Google Scholar]
  21. Papke R. L., Oswald R. E. Mechanisms of noncompetitive inhibition of acetylcholine-induced single-channel currents. J Gen Physiol. 1989 May;93(5):785–811. doi: 10.1085/jgp.93.5.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pedersen S. E., Cohen J. B. d-Tubocurarine binding sites are located at alpha-gamma and alpha-delta subunit interfaces of the nicotinic acetylcholine receptor. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2785–2789. doi: 10.1073/pnas.87.7.2785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Sine S. M., Steinbach J. H. Acetylcholine receptor activation by a site-selective ligand: nature of brief open and closed states in BC3H-1 cells. J Physiol. 1986 Jan;370:357–379. doi: 10.1113/jphysiol.1986.sp015939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sine S. M., Steinbach J. H. Activation of a nicotinic acetylcholine receptor. Biophys J. 1984 Jan;45(1):175–185. doi: 10.1016/S0006-3495(84)84146-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sine S. M., Steinbach J. H. Activation of acetylcholine receptors on clonal mammalian BC3H-1 cells by low concentrations of agonist. J Physiol. 1986 Apr;373:129–162. doi: 10.1113/jphysiol.1986.sp016039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Takeda K., Trautmann A. A patch-clamp study of the partial agonist actions of tubocurarine on rat myotubes. J Physiol. 1984 Apr;349:353–374. doi: 10.1113/jphysiol.1984.sp015160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wada E., Wada K., Boulter J., Deneris E., Heinemann S., Patrick J., Swanson L. W. Distribution of alpha 2, alpha 3, alpha 4, and beta 2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: a hybridization histochemical study in the rat. J Comp Neurol. 1989 Jun 8;284(2):314–335. doi: 10.1002/cne.902840212. [DOI] [PubMed] [Google Scholar]
  29. Wada K., Ballivet M., Boulter J., Connolly J., Wada E., Deneris E. S., Swanson L. W., Heinemann S., Patrick J. Functional expression of a new pharmacological subtype of brain nicotinic acetylcholine receptor. Science. 1988 Apr 15;240(4850):330–334. doi: 10.1126/science.2832952. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES