Skip to main content
Log in

Copper Ions Reduce the Effect of Protons on Desensitization of Glycine Receptors

  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

Chloride current (IGly) evoked by the rapid (600 msec) application of glycine on isolated pyramidal neurons of the rat hippocampus was recorded using the patch clamp technique. We studied the effect of individual or combined application of copper ions (Cu2+) and protons (H+) on IGly. It was found that both Cu2+ (10 μM) and H+ (pH 7.0 and 6.0) applied separately caused a fast and reversible effect on IGly that included two components: a decrease in peak amplitude (Ipeak) and a decrease in the desensitization time constant (τdes). During combined application, the effects on Ipeak were additive, which indicates the independence of the mechanisms of these effects. At the same time, the effect of combined application of Cu2+ and H+ on τdes was not additive and sometimes a slowdown of the total desensitization was observed. The latter result suggests that H+ and Cu2+ can play the role of mutual antagonists when they affect the desensitization of GlyR.

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.

Similar content being viewed by others

References

  1. Shuvaev AN, Salmin VV, Kuvacheva NV, Pozhilenkova EA, Salmina AB. Modern tendencies in the development of the patch-clamp technique: new opportunities for neuropharmacology and neurobiology. Ann. Klin. Eksp. Nevrol. 2015;9(4): 54-58.

    Google Scholar 

  2. Bukanova JV, Solntseva EI, Kondratenko RV, Skrebitsky VG. The influence of acidic media on the effect of beta-amyloid peptide on the function of glycine receptor in hippocampal neurons. Neurochem. Int. 2017;110):69-74.

    Article  Google Scholar 

  3. Chen Z, Dillon GH, Huang R. Identification of residues critical for Cu2+-mediated inhibition of glycine alpha1 receptors. Neuropharmacology. 2006;51(4):701-708.

    Article  CAS  PubMed  Google Scholar 

  4. Chen Z, Huang R. Identification of residues mediating inhibition of glycine receptors by protons. Neuropharmacology. 2007;52(8):1606-1615.

    Article  CAS  PubMed  Google Scholar 

  5. Delgado R, Vergara C, Wolff D. Divalent cations as modulators of neuronal excitability: emphasis on copper and zinc. Biol. Res. 2006;39(1):173-182.

    Article  CAS  PubMed  Google Scholar 

  6. Gaier ED, Eipper BA, Mains RE. Copper signaling in the mammalian nervous system: synaptic effects. J. Neurosci. Res. 2013;91(1):2-19.

    CAS  PubMed  Google Scholar 

  7. Gielen M, Thomas P, Smart TG. The desensitization gate of inhibitory Cys-loop receptors. Nat. Commun. 2015;6:6829. https://doi.org/10.1038/ncomms7829

  8. Gründer S, Chen X. Structure, function, and pharmacology of acid-sensing ion channels (ASICs): focus on ASIC1a. Int. J. Physiol. Pathophysiol. Pharmacol. 2010;2(2):73-94.

    PubMed  PubMed Central  Google Scholar 

  9. Lynch JW. Molecular structure and function of the glycine receptor chloride channel. Physiol. Rev. 2004;84(4):1051-1095.

    Article  CAS  PubMed  Google Scholar 

  10. Mathie A, Sutton GL, Clarke CE, Veale EL. Zinc and copper: pharmacological probes and endogenous modulators of neuronal excitability. Pharmacol. Ther. 2006;111(3):567-583.

    Article  CAS  PubMed  Google Scholar 

  11. Reeh PW, Steen KH. Tissue acidosis in nociception and pain. Prog. Brain Res. 1996;113:143-151.

    Article  CAS  PubMed  Google Scholar 

  12. Słupski J, Cubała WJ, Górska N, Gałuszko-Węgielnik M, Wiglusz MS. Role of copper in depression. Relationship with ketamine treatment. Med. Hypotheses. 2018;119:14-17.

    Article  PubMed  Google Scholar 

  13. Song YP, Schlesinger F, Ragancokova D, Calixto R, Dengler R, Krampfl K. Changes in extracellular pH affect glycine receptor channels expressed in HEK 293 cells. Eur. J. Pharmacol. 2010;636(1-3):59-64.

    Article  CAS  PubMed  Google Scholar 

  14. Xu TL, Gong N. Glycine and glycine receptor signaling in hippocampal neurons: diversity, function and regulation. Prog. Neurobiol. 2010;91(4):349-361.

    Article  CAS  PubMed  Google Scholar 

  15. Yevenes GE, Zeilhofer HU. Allosteric modulation of glycine receptors. Br. J. Pharmacol. 2011;164(2):224-236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. I. Solntseva.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 6, pp. 736-740, June, 2020

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Solntseva, E.I., Bukanova, J.V., Kondratenko, R.V. et al. Copper Ions Reduce the Effect of Protons on Desensitization of Glycine Receptors. Bull Exp Biol Med 169, 791–794 (2020). https://doi.org/10.1007/s10517-020-04980-w

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-020-04980-w

Key Words

Navigation