title: Ionizing radiation induces migration of glioblastoma cells by activating BK K(+) channels.
abstract: OBJECTIVE
  Glioblastoma cells express high levels of Ca(2+)-activated BK K(+) channels which have been proposed to be indispensable for glioblastoma proliferation and migration. Since migration of glioblastoma cells is reportedly stimulated by ionizing radiation (IR), we tested for an IR-induced increase in BK channel activity and its effect on cell migration.
  
  
  METHODS
  T98G and U87MG cells were X-ray-irradiated with 0-2 Gy, BK channel activity was assessed by patch-clamp recording, migration by trans-well migration assay, and activation of the Ca(2+)/calmodulin-dependent kinase II (CaMKII) by immunoblotting.
  
  
  RESULTS
  IR dose-dependently stimulated migration of glioblastoma cells which was sensitive to the BK channel inhibitor paxilline. Ca(2+)-permeabilization of T98G cells activated up to 350 BK channels per cells. Importantly, IR stimulated an increase in BK channel open probability but did not modify the total number of channels. Moreover, IR activated CaMKII in a paxilline-sensitive manner. Finally, inhibition of CaMKII by KN-93 abolished the IR-stimulated migration.
  
  
  CONCLUSIONS
  We conclude that IR stimulates BK channel activity which results in activation of CaMKII leading to enhanced glioblastoma cell migration.
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacy, University of Tübingen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Steinle
authors.forename: Daniela
authors.initials: D
authors.lastname: Palme
authors.forename: Milan
authors.initials: M
authors.lastname: Misovic
authors.forename: Justine
authors.initials: J
authors.lastname: Rudner
authors.forename: Klaus
authors.initials: K
authors.lastname: Dittmann
authors.forename: Robert
authors.initials: R
authors.lastname: Lukowski
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Huber
mesh_terms: D001596:Benzylamines / Q000494:pharmacology; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects*; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism / Q000528:radiation effects*; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism / Q000528:radiation effects*; D011839:Radiation, Ionizing; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides