Cellular and Molecular Neurobiology

, Volume 25, Issue 8, pp 1185–1194 | Cite as

Cyclic Nucleotides Induce Long-Term Augmentation of Glutamate-Activated Chloride Current in Molluscan Neurons

  • Julia V. BukanovaEmail author
  • Elena I. Solntseva
  • Vladimir G. Skrebitsky


  1. 1.

    Literature data indicate that serotonin induces the long-term potentiation of glutamate (Glu) response in molluscan neurons. The aim of present work was to elucidate whether cyclic nucleotides can cause the same effect.

  2. 2.

    Experiments were carried out on isolated neurons of the edible snail (Helix pomatia) using a two-microelectrode voltage-clamp method.

  3. 3.

    In the majority of the cells examined, the application of Glu elicited a Cl-current. The reversal potential (Er) of this current lied between −35 and −55 mV in different cells.

  4. 4.

    Picrotoxin, a blocker of Cl-channels, suppressed this current equally on both sides of Er. Furosemide, an antagonist of both Cl-channels and the Na+/K+/Cl-cotransporter, had a dual effect on Glu-response: decrease in conductance, and shift of Er to negative potentials.

  5. 5.

    A short-term (2 min) cell treatment with 8-Br-cAMP or 8-Br-cGMP caused long-term (up to 30 min) change in Glu-response. At a holding potential of −60 mV, which was close to the resting level, an increase in Glu-activated inward current was observed. This potentiation seems to be related to the right shift of Er of Glu-activated Cl-current rather than to the increase in conductance of Cl-channels. The blocking effect of picrotoxin rested after 8-Br-cAMP treatment.

  6. 6.

    The change in the Cl-homeostasis as a possible mechanism for the observed effect of cyclic nucleotides is discussed.



cyclic AMP cyclic GMP potentiation glutamate response chloride current molluscan neurons 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Antonov, I., Antonova, I., Kandel, E. R., and Hawkins, R. D. (2003). Activity-dependent presynaptic facilitation and Hebbian LTP are both required and interact during classical conditioning in Aplysia. Neuron 37:135–147.CrossRefPubMedGoogle Scholar
  2. Bachmann, O., Wuchner, K., Rossmann, H., Leipziger, J., Osikowska, B., Colledge, W. H., Ratcliff, R., Evans, M. J., Gregor, M., and Seilder, U. (2003). Expression and regulation of the Na+-K+-2Cl- cotransporter NKCC1 in the normal and CFTR-deficient murine colon. J. Physiol. 549:525–536.CrossRefPubMedGoogle Scholar
  3. Balaban, P. M., Korshunova, T. A., and Bravarenko, N. L. (2004). Postsynaptic calcium contributes to reinforcement in a three-neuron network exhibiting associative plasticity. Eur. J. Neurosci. 19:227–233.CrossRefPubMedGoogle Scholar
  4. Bolshakov, V. Y., Gapon, S., and Magazanik, L. G. (1991). Different types of glutamate receptors in isolated and identified neurons of the mollusc Planorbarius Corneus. J. Physiol. 439:15–35.PubMedGoogle Scholar
  5. Borisova, O. V., and Skrebitsky, V. G. (1991). Long-term enhancement of synaptic efficiency in Helix brain. In: Sakharov, D., and Winlow, W. (eds.), Simpler Nervous Systems. Studies in Neuroscience, Manchester University Press, pp. 213–226.Google Scholar
  6. Bravarenko, N. I., Korshunova, T. A., Malyshev, A. Y., and Balaban, P. M. (2003). Synaptic contact between mechanosensory neuron and withdrawal interneuron in terrestrial snail is mediated by L-glutamate-like transmitter. Neurosci. Lett. 341:237–240.CrossRefPubMedGoogle Scholar
  7. Chitwood, R. A., Li, Q., and Glanzman, D. L. (2001). Serotonin facilitates AMPA-type responses in isolated siphon motor neurons of Aplysia in culture. J. Physiol. 534:501–510.CrossRefPubMedGoogle Scholar
  8. Collin, C., Devane, W. A., Dahl, D., Lee, C.-J., Axelrod, J., and Alkon, D. (1995). Long-term synaptic transformation of hippocampal CA1 γ-aminobutyric acid synapses and the effect of anandamide. Proc. Natl. Acad. Sci. USA 92:10167–10171.PubMedGoogle Scholar
  9. Dale, N., and Kandel, E. R. (1993). L-Glutamate may be the fast excitatory transmitter of Aplysia sensory neurons. Proc. Natl. Acad. Sci. USA 90:7163–7167.PubMedGoogle Scholar
  10. Delpire, E. (2000). Cation-chloride cotransporters in neuronal communication. News Physiol. Sci. 15:309–312.PubMedGoogle Scholar
  11. Delporte, C., Winand, J., Poloczek, P., and Christophe, J. (1993). Regulation of Na-K-Cl cotransport, Na, K-adenosine triphosphatase, and Na/H exchanger in human neuroblastoma NB-OK-1 cells by atrial natriuretic peptide. Endocrinology 133:77–82.CrossRefPubMedGoogle Scholar
  12. Di Fulvio, M., Lincoln, T. M., Lauf, P. K., and Adragna, N. C. (2001). Protein kinase G regulate potassium chloride cotransporter-expression in primary cultures of rat vascular smooth muscle cells. J. Biol. Chem. 276:21046–21052.PubMedGoogle Scholar
  13. Etter, A., Cully, D. F., Liu, K. K., Reiss, B., Vassilatis, D. K., Schaeffer, J. M., and Arena, J. P. (1999). Picrotoxin blockade of invertebrate glutamate-gated chloride channels: Subunit dependence and evidence for binding within the pore. J. Neurochem. 72:318–326.PubMedGoogle Scholar
  14. Eusebi, F., Palmieri, P., and Picardo, M. (1978). Action of glutamic acid and of some glutamate analogues on the molluscan central neurons. Experientia 34:867–868.CrossRefPubMedGoogle Scholar
  15. Gusev, P. A., and Alkon, D. L. (2001). Intracellular correlates of spatial memory acquisition in hippocampal slices: long-term disinhibition of CA1 pyramidal cells. J. Neurophysiol. 86:881–899.PubMedGoogle Scholar
  16. Kehoe, J., and Vulfius, C. (2000). Independence of and interactions between GABA-, glutamate-, and acetylcholine-activated Cl conductance in Aplysia neurons. J. Neurosci. 20:8585–8596.PubMedGoogle Scholar
  17. Lewin, M. R., and Walters, E. T. (1999). Cyclic GMP pathway is critical for inducing long-term sensitization of nociceptive sensory neurons. Nature Neurosci. 2:18–23.PubMedGoogle Scholar
  18. Lytle, C. (1997). Activation of the avian erythrocyte Na-K-Cl cotransport protein by cell shrinkage, cAMP, fluoride, and calyculin-A involves phosphorylation at common sites. J. Biol. Chem. 272:15063–15077.CrossRefGoogle Scholar
  19. Lu, Y.-F., Kandel, E. R., and Hawkins, R. D. (1999). Nitric oxide signalling contributes to late-phase LTP and CREB phosphorylation in the hippocampus. J. Neurosci. 19:10250–10261.PubMedGoogle Scholar
  20. Lu, Y.-F., and Hawkins, R. D. (2002). Ryanodine receptors contribute to cGMP-induced late-phase LTP and CREB phosphorylation in the hippocampus. J. Neurophysiol. 88:1270–1278.PubMedGoogle Scholar
  21. Milner, B., Squire, L. R., and Kandel, E. R. (1998). Cognitive neuroscience and the study of memory. Neuron 20:445–468.CrossRefPubMedGoogle Scholar
  22. Narumi, S., and Miyamoto, E. (1974). Activation and phosphorylation of carbonic anhydrase by adenosine 3′,5′-monophosphate-dependent protein kinases. Biochem. Biophys. Acta. 350:215–224.PubMedGoogle Scholar
  23. Nicoll, R. A. (1978). The blockade of GABA mediated responses in the frog spinal cord by ammonium ions and furosemide. J. Physiol. 283:121–132.PubMedGoogle Scholar
  24. Niisato, N., Nishino, H., Nishio, K., and Marunaka, Y. (2004). Cross talk of cAMP and flavone in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel and Na+/K+/2Cl- cotransporter in renal epithelial A6 cells. Biochem. Pharmacol. 67:795–801.CrossRefPubMedGoogle Scholar
  25. O'Donnel, M. E., and Owen, N. E. (1986). Role of cyclic GMP in atrial natriuretic factor stimulation of Na+,K+,Cl- cotransport in vascular smooth muscle cells. J. Biol. Chem. 261:15461–15466.Google Scholar
  26. Paulsen, O., and Moser, E. R. (1998). A model of hippocampal memory encoding and retrieval: GABAergic control of synaptic plasticity. Trends Neurosci. 21:273–278.CrossRefPubMedGoogle Scholar
  27. Russel, J. M. (2000). Sodium-potassium-chloride cotransport. Physiol. Rev. 80:211–276.Google Scholar
  28. Sawada, M., Hara, N., Ito, I., and Maeno, T. (1984). Ionic mechanism of a hyperpolarizing glutamate effect on two identified neurons in the buccal ganglion of Aplysia. J. Neurosci. Res. 11:91–103.CrossRefPubMedGoogle Scholar
  29. Son, H., Lu, Y.-F., Zhuo, M., Arancio, O., Kandel, E. R., and Hawkins, R. D. (1998). The specific role of cGMP in hippocampal LTP. Learn. Mem. 5:231–245.PubMedGoogle Scholar
  30. Staley, K. J., Soldo, B. L., and Proctor, W. R. (1995). Ionic mechanisms of neuronal excitation by inhibitory CABAA receptors. Science 269:977–981.PubMedGoogle Scholar
  31. Sun, M.-K., and Alkon, D. L. (2002). Carbonic anhydrase gating of attention: memory therapy and enhancement. Trends Pharmacol. Sci. 23:83–89.CrossRefPubMedGoogle Scholar
  32. Yu, T. P., McKinney, S., Lester, H. A., and Davidson, N. (2001). Gamma-aminobutyric acid type A receptors modulate cAMP-mediated long-term potentiation and long-term depression at monosynaptic CA3-CA1 synapses. Proc. Natl. Acad. Sci. 98:5264–5269.PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Julia V. Bukanova
    • 1
    Email author
  • Elena I. Solntseva
    • 1
  • Vladimir G. Skrebitsky
    • 1
  1. 1.Russian Academy of Medical SciencesBrain Research InstituteMoscowRussia

Personalised recommendations