Skip to main content
Log in

The effects of cAMP, Ca2+, and phorbol esters on ouabain-induced depression of acetylcholine responses inHelix neurons

Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Summary

  1. 1.

    Using internal perfusion and concentration-clamp procedures applied toHelix neurons, the effects of cAMP, Ca2+, and phorbol esters on ouabain-induced depression of acetylcholine Cl-dependent responses were determined.

  2. 2.

    Intracellular cAMP (10−4 M) depressed those acetylcholine responses which were blocked by ouabain but had no effect on ouabain-insensitive acetylcholine responses. In the presence of elevated intracellular cAMP, ouabain had no further depressant effect on these acetylcholine responses. Both elevated cAMP and ouabain reduced the acetylcholine response without altering the current-voltage curves.

  3. 3.

    An increase in intracellular Ca2+ concentration depressed the amplitude of current induced by application of acetylcholine in neurons with ouabain-sensitive responses and shifted the dose-response relationship to the right. However, elevated Ca2+ did not reduce the maximal response induced by acetylcholine, nor did it prevent the reduction of that response by ouabain.

  4. 4.

    12-O-Tetradecanoilphorbol-13-acetate (TPA), a potent stimulator of protein kinase C activity, caused depression of both the ouabain-sensitive and the ouabain-insensitive acetylcholine responses. The inhibitory effect of TPA was markedly enhanced after addition of ATP to the intracellular medium and was greatly reduced by cooling to 5°C. The blocking effect of ouabain, however, reamined in the presence of TPA.

  5. 5.

    These observations are consistent with the hypothesis that the depression of acetylcholine induced Cl - responses inHelix neurons is a result of an increase in intracellular cAMP concentration but is unrelated to activation of protein kinase C or increases in intracellular Ca2+.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams, P. R. and Brown, D. A. (1986). Effects of phorbol ester on slow potassium currents of bullfrog ganglion cells.Biophys. J. 49215–220.

    Google Scholar 

  • Akaike, N., Inoue, M., and Krishtal, O. A. (1986). “Concentration clamp” study of GABA-induced chloride current kinetics in frog sensory neurons.J. Physiol. (Lond.)397171–185.

    Google Scholar 

  • Akopyan, A. R., Chimeris, N. K., Ilyin, V. Z. and Veprinzev, B. N. (1980). Serotinin, dopamine and intracellular cyclic AMP inhibit the responses of nicotinic cholinergic membrane in snail neurons.Brain Res. 201480–484.

    Google Scholar 

  • Arvanov, V. L., and Ayrapetyan, S. N. (1980). The action of ouabain on the cholinoreceptors of snail giant neuronal membrane.Rep. Acad. Sci. USSR 251222–226.

    Google Scholar 

  • Arvanov, V. L., Maginyan, S. B., and Ayrapetyan, S. N. (1984). On the inhibitory action of K-free solution on Cl-dependent ACh membrane responses.Rep. Acad. Sci. USSR 78 141–144.

    Google Scholar 

  • Arvanov, V. L., Bregestovski, P. D., and Ayrapetyan, S. N. (1990). Effect of ouabain on acetylcholine activated Cl-channels in isolated Helix neurons.Biol. Membr. (in press).

  • Arvanov, V. L., Ovakimyan, K. S., Stepanyan, A. S., and Ayrapetyan, S. N. (1992). Oubain blocks some rapid concentration-induced clamp acetylcholine responses onHelix neurons.Cell. Mol. Neurobiol. 12xxx-xxx.

    Google Scholar 

  • Ayrapetyan, S. N., and Arvanov, V. L. (1988). The metabolic regulation of membrane chemosensitivity. InNeurobiology of Invertebrates (J. Salanki, Ed.),Symp. Biol. Hung., Tihani 36669–684.

    Google Scholar 

  • Ayrapetyan, S. N., Sulamanian, M. A., Sugian, A. A., and Dadalian, S. S. (1984). Autoregulation of electrogenic sodium pump.Cell. Mol. Neurobiol. 4367–383.

    Google Scholar 

  • Ayrapetyan, S. N., Arvanov, V. L., Maginyan, S. B., and Azatyan, K. V. (1985). Further study of the correlation between Na-pump activity and membrane chemonsensitivity.Cell. Mol. Neurobiol. 5231–243.

    Google Scholar 

  • Ayrapetyan, S. N., Arvanov, V. L., and Maginyan, S. B. (1988). The pharmacological characteristics of two types of cholinoreceptors in the membrane of dialyzed neurons.Comp. Biochem. Physiol. 90C29–39.

    Google Scholar 

  • Bregestovski, P. D., and Arvanov, V. L. (1988). Effect of ouabain on characteristics of ACh activated ionic channels in Helix neurons. InII Allunion Congress on Neuroscience, Kiev (P. Kostyuk, Ed.), pp. 19-21.

  • Chemeris, N. K., Kazachenko, V. N., Kislov, A. N., and Kurchikov, A. A. (1982). Inhibition of acetylcholine responses by intracellular calcium inLumnaea stagnalis neurons.J. Physiol. (Lond.)3231–19.

    Google Scholar 

  • Eusebi, F., Grassi, F., Nervi, C., Caporale, C., Adamo, S., Zani, B., and Molinaro, M. (1987). Acetylcholine may regulate its own nicotinic receptor-channel through the C-kinase system.Proc. R. Soc. Lond. 230B355–365.

    Google Scholar 

  • Huganir, R. L., Delcow, A. H., Greengard, P., and Hess, G. P. (1986). Phosporilation of the nicotinic acetylcholine receptor regulates its rate of desensitization.Nature (Lond.) 321774–776.

    Google Scholar 

  • Kaczmarek, L. K. (1986). Phorbol ester, protein phosphorilaton and the regulation of neuronal ion channels.J. Exp. Biol. 124375–392.

    Google Scholar 

  • Kanamoni, T., Hazakawa, T., Nagatsu, T. (1976). Characterization of protein kinases from bovine parotid glands. The effect of tolbutamide and its derivate on these partially purified enzymes.Biochim. Biophys. Acta 429147–162.

    Google Scholar 

  • Kiskin, N. I., Krishtal, O. A., and Tsyndrenko, A. (1986). Excitatory amino acid receptors in hippocampal neurons: Kainate fails to desensitize them.Neurosci. Lett. 63225–230.

    Google Scholar 

  • Kostyuk, P. G., Krishtal, O. A., and Pidoplichko, V. L. (1975). Effects of internal fluoride and phosphate on membrane currents during intracellular dialyses of nerve cells.Nature (Lond.)257691–693.

    Google Scholar 

  • Nishizuka, Y. (1984). The role of protein kinase C in cell surface signal transduction and tumour promotion.Nature (Lond).308693–698.

    Google Scholar 

  • Oron, Y. Dascal, N., Nadler, E., and Lupu, M. (1985). Inositol 1,4,5-triphosphate mimics muscarinic response in Xenopus Occytes.Nature (Lond.)313141–143.

    Google Scholar 

  • Rosenbrock, H. H. (1960). An automatic method for finding the greatest or least value of a function.Comput. J. 3175–184.

    Google Scholar 

  • Vicentini, L. M., Virgillo, F., Ambiosini, A., Pozzar, T., and Meldolesi, J. (1985). Tumour promoter phorbol 12-meristate, 13-acetate inhibits phosphoinositide hydrolysis and cytosolic Ca rise induced by activation of muscarinic receptors in PC 12 cells.Biochem. Biophys. Res. Commun. 127310–317.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arvanov, V.L., Stepanyan, A.S. & Ayrapetyan, S.N. The effects of cAMP, Ca2+, and phorbol esters on ouabain-induced depression of acetylcholine responses inHelix neurons. Cell Mol Neurobiol 12, 153–161 (1992). https://doi.org/10.1007/BF00713369

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00713369

Key words

Navigation