Skip to main content
NCBI 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
. 1987 Nov;84(22):8155–8159. doi: 10.1073/pnas.84.22.8155

Cyclic AMP regulates the proportion of functional acetylcholine receptors on chicken ciliary ganglion neurons.

J F Margiotta 1, D K Berg 1, V E Dionne 1
PMCID: PMC299497  PMID: 2446319

Abstract

Previous studies have shown that the number of functional acetylcholine receptors (AcChoRs) on chicken ciliary ganglion neurons in culture is considerably smaller than the total number of AcChoRs detected on the neurons by labeled receptor probes. Here we use patch-clamp recording to show that a cAMP-dependent process enhances the AcCho response of the neurons by a mechanism likely to involve an increase in the number of functional AcChoRs. The increase occurs without requiring protein synthesis and without involving a detectable increase in the total number of AcChoRs on the cell surface measured with a labeled receptor probe. The results imply that the neurons have functional and nonfunctional pools of AcChoRs and that functional receptors can be recruited from intracellular receptors or from nonfunctional receptors on the cell surface by a cAMP-dependent process. A cAMP-dependent regulation of the number of functional neurotransmitter receptors would provide a reversible mechanism by which cell-cell interactions could modulate synaptic transmission in the nervous system.

Full text

PDF
8155

Selected References

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

  1. Albuquerque E. X., Deshpande S. S., Aracava Y., Alkondon M., Daly J. W. A possible involvement of cyclic AMP in the expression of desensitization of the nicotinic acetylcholine receptor. A study with forskolin and its analogs. FEBS Lett. 1986 Apr 7;199(1):113–120. doi: 10.1016/0014-5793(86)81235-2. [DOI] [PubMed] [Google Scholar]
  2. Armstrong D., Eckert R. Voltage-activated calcium channels that must be phosphorylated to respond to membrane depolarization. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2518–2522. doi: 10.1073/pnas.84.8.2518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bean B. P., Nowycky M. C., Tsien R. W. Beta-adrenergic modulation of calcium channels in frog ventricular heart cells. 1984 Jan 26-Feb 1Nature. 307(5949):371–375. doi: 10.1038/307371a0. [DOI] [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. Browning M. D., Huganir R., Greengard P. Protein phosphorylation and neuronal function. J Neurochem. 1985 Jul;45(1):11–23. doi: 10.1111/j.1471-4159.1985.tb05468.x. [DOI] [PubMed] [Google Scholar]
  6. Brum G., Flockerzi V., Hofmann F., Osterrieder W., Trautwein W. Injection of catalytic subunit of cAMP-dependent protein kinase into isolated cardiac myocytes. Pflugers Arch. 1983 Jul;398(2):147–154. doi: 10.1007/BF00581064. [DOI] [PubMed] [Google Scholar]
  7. Cachelin A. B., de Peyer J. E., Kokubun S., Reuter H. Ca2+ channel modulation by 8-bromocyclic AMP in cultured heart cells. Nature. 1983 Aug 4;304(5925):462–464. doi: 10.1038/304462a0. [DOI] [PubMed] [Google Scholar]
  8. DEL CASTILLO J., KATZ B. Interaction at end-plate receptors between different choline derivatives. Proc R Soc Lond B Biol Sci. 1957 May 7;146(924):369–381. doi: 10.1098/rspb.1957.0018. [DOI] [PubMed] [Google Scholar]
  9. Dionne V. E., Leibowitz M. D. Acetylcholine receptor kinetics. A description from single-channel currents at snake neuromuscular junctions. Biophys J. 1982 Sep;39(3):253–261. doi: 10.1016/S0006-3495(82)84515-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Feltz A., Trautmann A. Desensitization at the frog neuromuscular junction: a biphasic process. J Physiol. 1982 Jan;322:257–272. doi: 10.1113/jphysiol.1982.sp014036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fesenko E. E., Kolesnikov S. S., Lyubarsky A. L. Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment. Nature. 1985 Jan 24;313(6000):310–313. doi: 10.1038/313310a0. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Halvorsen S. W., Berg D. K. Affinity labeling of neuronal acetylcholine receptor subunits with an alpha-neurotoxin that blocks receptor function. J Neurosci. 1987 Aug;7(8):2547–2555. [PMC free article] [PubMed] [Google Scholar]
  14. Halvorsen S. W., Berg D. K. Identification of a nicotinic acetylcholine receptor on neurons using an alpha-neurotoxin that blocks receptor function. J Neurosci. 1986 Nov;6(11):3405–3412. doi: 10.1523/JNEUROSCI.06-11-03405.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Huganir R. L., Delcour A. H., Greengard P., Hess G. P. Phosphorylation of the nicotinic acetylcholine receptor regulates its rate of desensitization. Nature. 1986 Jun 19;321(6072):774–776. doi: 10.1038/321774a0. [DOI] [PubMed] [Google Scholar]
  16. Huganir R. L., Greengard P. cAMP-dependent protein kinase phosphorylates the nicotinic acetylcholine receptor. Proc Natl Acad Sci U S A. 1983 Feb;80(4):1130–1134. doi: 10.1073/pnas.80.4.1130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. KATZ B., THESLEFF S. A study of the desensitization produced by acetylcholine at the motor end-plate. J Physiol. 1957 Aug 29;138(1):63–80. doi: 10.1113/jphysiol.1957.sp005838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Katz B., Miledi R. The statistical nature of the acetycholine potential and its molecular components. J Physiol. 1972 Aug;224(3):665–699. doi: 10.1113/jphysiol.1972.sp009918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Levitan I. B. Phosphorylation of ion channels. J Membr Biol. 1985;87(3):177–190. doi: 10.1007/BF01871217. [DOI] [PubMed] [Google Scholar]
  20. Margiotta J. F., Berg D. K. Enkephalin and substance P modulate synaptic properties of chick ciliary ganglion neurons in cell culture. Neuroscience. 1986 May;18(1):175–182. doi: 10.1016/0306-4522(86)90186-7. [DOI] [PubMed] [Google Scholar]
  21. McHugh E. M., McGee R., Jr Direct anesthetic-like effects of forskolin on the nicotinic acetylcholine receptors of PC12 cells. J Biol Chem. 1986 Mar 5;261(7):3103–3106. [PubMed] [Google Scholar]
  22. Middleton P., Jaramillo F., Schuetze S. M. Forskolin increases the rate of acetylcholine receptor desensitization at rat soleus endplates. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4967–4971. doi: 10.1073/pnas.83.13.4967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nakamura T., Gold G. H. A cyclic nucleotide-gated conductance in olfactory receptor cilia. 1987 Jan 29-Feb 4Nature. 325(6103):442–444. doi: 10.1038/325442a0. [DOI] [PubMed] [Google Scholar]
  24. Nishi R., Berg D. K. Two components from eye tissue that differentially stimulate the growth and development of ciliary ganglion neurons in cell culture. J Neurosci. 1981 May;1(5):505–513. doi: 10.1523/JNEUROSCI.01-05-00505.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ogden D. C., Gray P. T., Colquhoun D., Rang H. P. Kinetics of acetylcholine activated ion channels in chick ciliary ganglion neurones grown in tissue culture. Pflugers Arch. 1984 Jan;400(1):44–50. doi: 10.1007/BF00670535. [DOI] [PubMed] [Google Scholar]
  26. Patrick J., Stallcup B. alpha-Bungarotoxin binding and cholinergic receptor function on a rat sympathetic nerve line. J Biol Chem. 1977 Dec 10;252(23):8629–8633. [PubMed] [Google Scholar]
  27. Patrick J., Stallcup W. B. Immunological distinction between acetylcholine receptor and the alpha-bungarotoxin-binding component on sympathetic neurons. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4689–4692. doi: 10.1073/pnas.74.10.4689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Reuter H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature. 1983 Feb 17;301(5901):569–574. doi: 10.1038/301569a0. [DOI] [PubMed] [Google Scholar]
  29. Role L. W. Substance P modulation of acetylcholine-induced currents in embryonic chicken sympathetic and ciliary ganglion neurons. Proc Natl Acad Sci U S A. 1984 May;81(9):2924–2928. doi: 10.1073/pnas.81.9.2924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sakmann B., Patlak J., Neher E. Single acetylcholine-activated channels show burst-kinetics in presence of desensitizing concentrations of agonist. Nature. 1980 Jul 3;286(5768):71–73. doi: 10.1038/286071a0. [DOI] [PubMed] [Google Scholar]
  31. Seamon K. B., Padgett W., Daly J. W. Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3363–3367. doi: 10.1073/pnas.78.6.3363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shuster M. J., Camardo J. S., Siegelbaum S. A., Kandel E. R. Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+ channels of Aplysia sensory neurones in cell-free membrane patches. 1985 Jan 31-Feb 6Nature. 313(6001):392–395. doi: 10.1038/313392a0. [DOI] [PubMed] [Google Scholar]
  33. Siegelbaum S. A., Camardo J. S., Kandel E. R. Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones. Nature. 1982 Sep 30;299(5882):413–417. doi: 10.1038/299413a0. [DOI] [PubMed] [Google Scholar]
  34. Smith M. A., Margiotta J. F., Franco A., Jr, Lindstrom J. M., Berg D. K. Cholinergic modulation of an acetylcholine receptor-like antigen on the surface of chick ciliary ganglion neurons in cell culture. J Neurosci. 1986 Apr;6(4):946–953. doi: 10.1523/JNEUROSCI.06-04-00946.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Stollberg J., Berg D. K. Neuronal acetylcholine receptors: fate of surface and internal pools in cell culture. J Neurosci. 1987 Jun;7(6):1809–1815. doi: 10.1523/JNEUROSCI.07-06-01809.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tzartos S. J., Rand D. E., Einarson B. L., Lindstrom J. M. Mapping of surface structures of electrophorus acetylcholine receptor using monoclonal antibodies. J Biol Chem. 1981 Aug 25;256(16):8635–8645. [PubMed] [Google Scholar]
  37. Whiting P. J., Lindstrom J. M. Purification and characterization of a nicotinic acetylcholine receptor from chick brain. Biochemistry. 1986 Apr 22;25(8):2082–2093. doi: 10.1021/bi00356a037. [DOI] [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