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Temperature-Induced Modulation of Voltage-Gated Ion Channels in Human Lung Cancer Cell Line A549 Using Automated Patch Clamp Technology

Conference paper
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Part of the IFMBE Proceedings book series (IFMBE, volume 68/3)

Abstract

In cancer cells specific ion channels exhibit altered channel expression, which can drive malignant and metastatic cell behavior. Hence, therapeutic strategies modulating ion channels prove to be promising in cancer therapeutics. Alterations in temperature, even small deviations from normothermia, may cause changes in electrophysiological processes, since activation and conductivity of various ion channels are temperature-dependent. In this pilot study, we focused on a basic understanding of the effects of temperature-alterations on voltage-gated ion channels of A549 cells using an automated patch-clamp system. The measurements were carried out in whole-cell voltage-clamped configuration applying test pulses between −60 and +60 mV. For positive voltages the ion-current curves showed an instantaneously increased conductance, followed by a slow current increase provoked by later activating voltage-gated ion channels, indicating the time-delayed response of additional channels. To investigate the temperature-dependent electrophysiological behavior, six cells (passages 7–10, n = 34) were examined at room temperature and normal body temperature. Compared to normal body temperature, reduced temperatures revealed a higher whole-cell current at negative voltages (63.4% (±18.5%), −60 mV) and lower currents (52.6% (±27.3%), +60 mV) at positive voltages, indicating a hypothermia-induced modulation of voltage-gated channels in the lung cancer cell line A549.

Keywords

Ion channels Non-small cell lung cancer Hypothermia 

Notes

Author’s Statement

The authors declare that they have no conflict of interest.

References

  1. 1.
    Ma X., Yu H.: Global Burden of Cancer. Yale J Biol Med 79(3–4), 8 –94 (2006).Google Scholar
  2. 2.
    Ramalingam S.S., Owonikoko T.K., Khuri F.R.: Lung cancer: New biological insights and recent therapeutic advances. CA Cancer J Clin 61(2), 91–112 (2011).Google Scholar
  3. 3.
    Manegold C., Thatcher N.: Survival improvement in thoracic cancer: progress from the last decade and beyond. Lung Cancer 57, Suppl 2:S3–S5 (2007).Google Scholar
  4. 4.
    Yang M., Brackenbury J.W.: Membrane potential and cancer progression. Front Physiol 4:185 (2013).Google Scholar
  5. 5.
    Rao V.R., Perez-Neut M., Kaja S., Gentile S.: Voltage-Gated Ion Channels in Cancer Cell Proliferation. Cancers (Basel) 7(2), 849–875 (2015).Google Scholar
  6. 6.
    Huang X., Jan L.Y.: Targeting Potassium channels in cancer. J Cell Biol 206(2), 151–62 (2014).Google Scholar
  7. 7.
    Pang C.L.K.: Hyperthermia in Oncology. CRC Press Tylor Francis Group, Boca Raton (2016).Google Scholar
  8. 8.
    Jha S., Sharma P.K., Malviya R.: Hyperthermia: Role and Risk Factor for Cancer Treatment. Achievements in the Life Sciences 10, 161–167 (2016).Google Scholar
  9. 9.
    Remani R., Ostapenko V.V., Akagi K., Bhattathiri V.N., Nair M.K., Tanaka Y.: Relation of transmembrane potential to cell survival following hyperthermia in HeLa cells. Cancer Letters 144, 117–123 (1999).Google Scholar
  10. 10.
    Kalamida D., Karagounis I.V., Mitrakas A., Kalamida S., Giatromanolaki A., Koukourakis M.I.: Fever-Range Hyperthermia vs. Hypothermia Effect on Cancer Cell Viability, Proliferation and HSP90 Expression. PLoS One 10(1), e0116021 (2015).Google Scholar
  11. 11.
    Speit G., Schütz P.: Hyperthermia-induced genotoxic effects in human A549 cells. Mutat Res 747–748:1–5 (2013).Google Scholar
  12. 12.
    Urban N., Beyersdorf F.: Hypothermia and its effect on tumor growth. Z Herz- Thorax- Gefäßchir 31, 222–227 (2017).Google Scholar
  13. 13.
    Sano M.E., Smith L.W.: The Behavior of Tumor Cells in Tissue Culture Subjected to Reduced Temperatures. Cancer Res 2, 32–39 (1942).Google Scholar
  14. 14.
    Peloquin J.B., Doering C.J., Rehak R., McRory J.E.: Temperature dependence of Cav1.4 calcium channel gating. Neuroscience 151(4), 1066–83 (2008).Google Scholar
  15. 15.
    Vandenberg J.I., Varghese A., Lu Y., Bursill J.A., Mahaut-Smith M.P., Huang C.L.: Temperature dependence of human ether-a-go-go-related gene K + currents. Am J Physiol Cell Physiol 291(1), C165–75 (2006).Google Scholar
  16. 16.
    Mauerhöfer M., Bauer C.K.: Effects of Temperature on Heteromeric Kv11.1a/1b and Kv11.3 Channels. Biophys J 111(3), 504–523 (2016).Google Scholar
  17. 17.
    Wawrzkiewicz-Jalowiecka A., Dworakowska B., Grzywna Z.J.: The temperature dependence of the BK channel activity – kinetics, thermodynamics, and long-range correlations. Biochim Biophys Acta 1859(10), 1805–1814 (2017).Google Scholar
  18. 18.
    Yang F., Zheng J.: High temperature sensitivity is intrinsic to voltage-gated potassium channels. Elife 3, e03255 (2014).Google Scholar
  19. 19.
    Khasawneh F.A., Thomas A., Thomas S.: Accidental Hypothermia. Hospital Physician 16–21 (2006).Google Scholar
  20. 20.
    Roth B.: Exposure to sparsely and densely ionizing irradiation results in an immediate activation of K+ channels in A549 cells and in human peripheral blood lymphocytes. (Doctoral Thesis). Technische Universität Darmstadt, Darmstadt (2014).Google Scholar
  21. 21.
    Gibhardt C.: Radiation induced activation of potassium-channels: The role of ROS and calcium. (Doctoral Thesis). Technische Universität Darmstadt, Darmstadt (2014).Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Institute of Health Care Engineering with European Testing Center of Medical DevicesGraz University of TechnologyGrazAustria
  2. 2.CBmed—Center for Biomarker Research in MedicineGrazAustria

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