Skip to main content

The influence of protons and zinc ions on the steady-state inactivation of Kv1.3 potassium channels

Abstract

Using the whole-cell patch-clamp technique, we investigated the influence of extracellular pH and zinc ions (Zn2+) on the steady-state inactivation of Kv1.3 channels expressed in human lymphocytes. The obtained data showed that lowering the extracellular pH from 7.35 to 6.8 shifted the inactivation midpoint (Vi) by 17.4 ± 1.12 mV (n = 6) towards positive membrane potentials. This shift was statistically significant (p < 0.05). Applying 100 μM Zn2+ at pH 6.8 further shifted the Vi value by 16.55 ± 1.80 mV (n = 6) towards positive membrane potentials. This shift was also statistically significant (p < 0.05). The total shift of the Vi by protons and Zn2+ was 33.95 ± 1.90 mV (n = 6), which was significantly higher (p < 0.05) than the shift caused by Zn2+ alone. The Zn2+-induced shift of the Vi at pH 6.8 was almost identical to the shift at pH = 7.35. Thus, the proton-and Zn2+-induced shifts of the Vi value were additive. The steady-state inactivation curves as a function of membrane voltage were compared with the functions of the steady-state activation. The total shift of the steady-state inactivation was almost identical to the total shift of the steady-state activation (32.01 ± 2.10 mV, n = 10). As a result, the “windows” of membrane potentials in which the channels can be active under physiological conditions were also markedly shifted towards positive membrane potentials. The values of membrane voltage and the normalised chord conductance corresponding to the points of intersection of the curves of steady-state activation and inactivation were also calculated. The possible physiological significance of the observed modulatory effects is discussed herein.

Abbreviations

gKnorm :

normalised relative chord conductance

gKSSnorm :

steady-state normalised relative chord conductance

ki :

steepness of the voltage dependence (inactivation)

kn :

steepness of the voltage dependence (activation)

pHo :

extracellular pH

TL:

human T lymphocytes

Vi :

inactivation midpoint

Vn :

activation midpoint

Zn2+ :

zinc ions

References

  1. Frederickson, C., Klitenick, M., Menton, W. and Kirpatrick, J. Cytoarchitectonic distribution of zinc in the hippocampus of man and the rat.Brain Res. 273 (1983) 335–339.

    Article  CAS  PubMed  Google Scholar 

  2. Harrison, N. and Gibbons, S. Zinc: an endogenous modulator of ligand and voltage-gated ion channels.Neuropharmacol. 33 (1994) 935–952.

    Article  CAS  Google Scholar 

  3. Lewis, R. and Cahalan, M. Potassium and calcium channels in lymphocytes.Annu. Rev. Immunol. 13 (1995) 623–653.

    Article  CAS  PubMed  Google Scholar 

  4. Teisseyre, A. Voltage-gated potassium channels in T lymphocytes-physiological role and changes in channel properties in diseases.Cell. Mol. Biol. Lett. 1 (1996) 337–351.

    CAS  Google Scholar 

  5. Shieh, Ch., Coghlan, M., Sullivan, J. and Gopalakrishan, M. Potassium channels: molecular defects, diseases and therapeutic opportunities.Pharmacol. Rev. 52 (2000) 557–593.

    CAS  PubMed  Google Scholar 

  6. Cahalan, M., Wulff, H. and Chandy, K. Molecular properties and physiological roles of ion channels in the immune system.J. Clin. Immunol. 21 (2001) 235–252.

    Article  CAS  PubMed  Google Scholar 

  7. Veh, R., Lichtinghagen, R., Sewing, S., Wunder, F., Grumbach, I. and Pongs, O. Immunohistochemical localization of five members of the Kv1 channel subunits: contrasting subcellular locations and neuron-specific co-localizations in rat brain.Eur. J. Neurosci. 7 (1995) 2189–2205.

    Article  CAS  PubMed  Google Scholar 

  8. Kupper, J., Prinz, A. and Fromherz, P. Recombinant Kv1.3 potassium channels stabilize tonic firing of cultured rat hippocampal neurons.Pflügers Arch. 443 (2002) 541–547.

    Article  CAS  PubMed  Google Scholar 

  9. Colley, B., Tucker, K. and Fadool, D. Comparison of modulation of Kv1.3 channel by two receptor tyrosine kinases in olfactory bulb neurons of rodents.Rec. Channels 10 (2004) 25–36.

    Google Scholar 

  10. Mackenzie, A., Chirakkal, H. and North, A. Kv1.3 potassium channels in human alveolar macrophages.Am. J. Physiol. Lung Cell. Mol. Physiol. 285 (2003) L862–L868.

    CAS  PubMed  Google Scholar 

  11. Speake, T., Kibble, J. and Brown, P. Kv1.1 and Kv1.3 channels contribute to the delayed-rectifying conductance in rat choroid plexus epithelial cells.Am. J. Physiol. Cell Physiol. 286 (2004) C611–C620.

    Article  CAS  PubMed  Google Scholar 

  12. Grunnet, M., Rasmussen, H., Hay-Schmidt, A. and Klaerke, D. The voltage-gated potassium channel subunit, Kv1.3, is expressed in epithelia.Biochim. Biophys. Acta 1616 (2003) 85–94.

    Google Scholar 

  13. Preuβat, K., Beetz, Ch., Schrey, M., Kraft, R., Wölfl, S., Kalff, R. and Patt, S. Expression of voltage-gated potassium channels Kv1.3 and Kv1.5 in human gliomas.Neurosci. Lett. 346 (2003) 33–36.

    Article  Google Scholar 

  14. Fraser, S., Grimes, J., Diss, J., Stewart, D., Dolly, J. and Djamgoz, M. Predominant expression of Kv1.3 voltage-gated K+ channel subunit in rat prostate cancer cell lines: electrophysiological, pharmacological and molecular characterisation.Pflügers Arch. 446 (2003) 559–571.

    Article  CAS  PubMed  Google Scholar 

  15. Teisseyre, A. and Mozrzymas, J.W. Inhibition of the activity of T lymphocyte Kv1.3 channels by extracellular zinc.Biochem. Pharmacol. 64 (2002) 595–607.

    Article  CAS  PubMed  Google Scholar 

  16. Teisseyre, A. and Mozrzymas, J.W. Influence of extracellular pH on the modulatory effect of zinc ions on Kv1.3 potassium channels.J. Physiol. Pharmacol. 57 (2006) 131–147.

    CAS  PubMed  Google Scholar 

  17. Teisseyre, A. and Mozrzymas, J.W. [Influence of pH on the modulatory effect of zinc ions on the activity of Kv1.3 potassium channels] Acta Universitatis Lodziensis, Folia Biologica et Oecologica [Proc. V-Polish wide Conference: “Electrophysiological techniques in investigations of bioelectrical phenomena: from ion channels to neuronal networks”], Łódź, Poland, 2006, 31–40.

  18. Deutsch, C. and Lee, S. Modulation of K+ currents in human lymphocytes by pH.J. Physiol. 413 (1989) 399–413.

    CAS  PubMed  Google Scholar 

  19. Hirano, T., Kuritani, T., Kishimoto, Y. and Yamamura, Y. T cell dependency of PWM-induced Ig production by B cells.J. Immunol. 119 (1977) 1235–1242.

    CAS  PubMed  Google Scholar 

  20. Grissmer, S., Nguyen, A. and Cahalan, M. Calcium-activated potassium channels in resting and activated human T lymphocytes.J. Gen. Physiol. 102 (1993) 601–630.

    Article  CAS  PubMed  Google Scholar 

  21. Hamill, O., Marty, A., Neher, E., Sakmann, B. and Sigworth, F. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.Pflügers Arch. 391 (1981) 85–100.

    Article  CAS  PubMed  Google Scholar 

  22. Somodi, S., Varga, Z., Hajdu, P., Starkus, J., Levy, D., Gaspar, R. and Panyi, G. PH-dependent modulation of Kv1.3 inactivation: role of His 399. Am. J. Physiol. Cell Physiol. 287 (2004) C1067–C1076.

    Article  CAS  PubMed  Google Scholar 

  23. Reardon, C. and Lucas, D. Heavy-metal mitogenesis: Zn and Hg induce cellular cytotoxicity and interferon production in murine T lymphocytes.Immunobiology 175 (1987) 455–469.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrzej Teisseyre.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Teisseyre, A., Mozrzymas, J.W. The influence of protons and zinc ions on the steady-state inactivation of Kv1.3 potassium channels. Cell Mol Biol Lett 12, 220–230 (2007). https://doi.org/10.2478/s11658-006-0067-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11658-006-0067-6

Key words

  • Zinc
  • Lymphocyte
  • Potassium channels
  • Patch-clamp
  • pH
  • Neuronal excitability