title: Low-dose photon irradiation alters cell differentiation via activation of hIK channels.
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 Ca(2+)-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 Ca(2+)-mediated signaling cascade because channel activation is suppressed by a strong cytosolic Ca(2+) buffer. The finding that an elevation of H2O2 causes an increase in the concentration of cytosolic Ca(2+) suggests that radicals, which emerge early in response to irradiation, trigger this Ca(2+) 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.
authors.affiliation: Department of Biology, Plant Membrane Biophysics, Technische Universität Darmstadt, Schnittspahnstrasse 3, 64287, Darmstadt, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Roth
authors.forename: Christine S
authors.initials: CS
authors.lastname: Gibhardt
authors.forename: Patrick
authors.initials: P
authors.lastname: Becker
authors.forename: Manuela
authors.initials: M
authors.lastname: Gebhardt
authors.forename: Jan
authors.initials: J
authors.lastname: Knoop
authors.forename: Claudia
authors.initials: C
authors.lastname: Fournier
authors.forename: Anna
authors.initials: A
authors.lastname: Moroni
authors.forename: Gerhard
authors.initials: G
authors.lastname: Thiel
mesh_terms: D020013:Calcium Signaling / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects; D016207:Cytokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000528:radiation effects*; D008564:Membrane Potentials; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000528:radiation effects; D017785:Photons; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors; D014162:Transfection
chemical_list: D016207:Cytokines; C090444:IK protein, human; D016877:Oxidants; D026902:Potassium Channel Blockers; D011993:Recombinant Fusion Proteins