title: Defective potassium currents in ataxia telangiectasia fibroblasts.
abstract: Similarities exist between the progressive cerebellar ataxia in ataxia telangiectasia (AT) patients and a number of neurodegenerative diseases in both mouse and man involving specific mutations in ion channels and/or ion channel activity. These relationships led us to investigate the possibility of defective ion channel activity in AT cells. We examined changes in the membrane potential of AT fibroblasts in response to extracellular cation addition and found that the ability of AT fibroblasts to depolarize in response to increasing concentrations of extracellular K+ is significantly reduced when compared with control fibroblasts. Electrophysiological measurements performed with a number of AT cell lines, as well as two matched sets of primary AT fibroblast cultures, reveal that outward rectifier K+ currents are largely absent in AT fibroblasts in comparison with control cells. These K+ current defects can be corrected in AT fibroblasts transfected with the full-length ATM cDNA. These data implicate, for the first time, a role for ATM in the regulation of K+ channel activity and membrane potential.
authors.affiliation: Department of Cancer Biology, GlaxoWellcome Research and Development, Research Triangle Park, North Carolina 27709 USA.
authors.forename: N
authors.initials: N
authors.lastname: Rhodes
authors.forename: T
authors.initials: T
authors.lastname: D'Souza
authors.forename: C D
authors.initials: CD
authors.lastname: Foster
authors.forename: Y
authors.initials: Y
authors.lastname: Ziv
authors.forename: D G
authors.initials: DG
authors.lastname: Kirsch
authors.forename: Y
authors.initials: Y
authors.lastname: Shiloh
authors.forename: M B
authors.initials: MB
authors.lastname: Kastan
authors.forename: P H
authors.initials: PH
authors.lastname: Reinhart
authors.forename: T M
authors.initials: TM
authors.lastname: Gilmer
mesh_terms: D001260:Ataxia Telangiectasia / Q000378:metabolism*; D002460:Cell Line; D004553:Electric Conductivity; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*
chemical_list: D015221:Potassium Channels; D011188:Potassium