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Low-dose photon irradiation alters cell differentiation via activation of hIK channels

  • Signaling and cell physiology
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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

To understand the impact of ionizing irradiation from diagnostics and radiotherapy on cells, we examined K+ channel activity before and immediately after exposing cells to X-rays. Already, low dose in the cGy range caused in adenocarcinoma A549 cells within minutes a hyperpolarization following activation of the human intermediate-conductance Ca2+-activated K+ channel (hIK). The response was specific for cells, which functionally expressed hIK channels and in which hIK activity was low before irradiation. HEK293 cells, which do not respond to X-ray irradiation, accordingly develop a sensitivity to this stress after heterologous expression of hIK channels. The data suggest that hIK activation involves a Ca2+-mediated signaling cascade because channel activation is suppressed by a strong cytosolic Ca2+ buffer. The finding that an elevation of H2O2 causes an increase in the concentration of cytosolic Ca2+ suggests that radicals, which emerge early in response to irradiation, trigger this Ca2+ signaling cascade. Inhibition of hIK channels by specific blockers clotrimazole and TRAM-34 slowed cell proliferation and migration in “wound” scratch assays; ionizing irradiation, in turn, stimulated the latter process presumably via its activation of the hIK channels. These data stress an indirect radiosensitivity of hIK channels with an impact on cell differentiation.

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Acknowledgments

This work was supported, in part, by the HIC-for-Fair project, the ESA-IBER project, the BMBF (project 02NUK017B), and the GRK 1657. We thank Dr. Atsushi Miyawaki (RIKEN Brain Science Institute) for calcium sensor YC3.60 and Sandro Conrad and Markus Löbrich (TU Darmstadt) for technical support during X-ray experiments and Franz Rödel (Uni. Frankfurt) and Marco Durante (GSI) for useful discussions. We are also grateful to continuous support from the NanIon team.

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Correspondence to Gerhard Thiel.

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ESM 1

Fig. S1 shows a transcription analysis of K+ channel genes in different cell lines. Fig. S2 shows that a sham-irradiation of A549 cells has no effect on membrane conductance (a). During long recordings A549 cells show a run down (b). Fig. S3 shows that challenging A549 cells with μM concentrations of H2O2 increases the hIK conductance in A549 cells. Fig. S4 shows the typical distribution of cell cycle states of A549 cells used in this study (a,b). Data in c and d show that ionizing irradiation (1Gy) has no impact on apoptosis of A549 cells. (PDF 604 kb)

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Roth, B., Gibhardt, C.S., Becker, P. et al. Low-dose photon irradiation alters cell differentiation via activation of hIK channels. Pflugers Arch - Eur J Physiol 467, 1835–1849 (2015). https://doi.org/10.1007/s00424-014-1601-4

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  • DOI: https://doi.org/10.1007/s00424-014-1601-4

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