title: Cells exposed to a huntingtin fragment containing an expanded polyglutamine tract show no sign of ion channel formation: results arguing against the ion channel hypothesis.
abstract: Ion channels formed by expanded polyglutamine tracts have been proposed to play an important role in the pathological processes leading to neurodegeneration in Huntington's disease and other CAG repeat diseases. We tested the capacity of a huntingtin fragment containing an expanded polyglutamine tract to form ion channels in two cell types. Whole cell current from Xenopus oocytes was recorded using two-electrode voltage-clamp technique, and whole cell current from CHO-K1 cells was recorded by patch-clamp technique. The fragment with an expanded polyglutamine sequence induced no change in the currents recorded in any of the two expression systems, indicating no changes in ion channel activity. The results therefore argue against the proposed hypothesis of expanded polyglutamines forming ion channels.
authors.affiliation: Department of Medical Genetics, University of Copenhagen, Copenhagen, Denmark. anm@imbg.ku.dk
authors.forename: Anne
authors.initials: A
authors.lastname: Nørremølle
authors.forename: Morten
authors.initials: M
authors.lastname: Grunnet
authors.forename: Lis
authors.initials: L
authors.lastname: Hasholt
authors.forename: Sven Asger
authors.initials: SA
authors.lastname: Sørensen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells / Q000378:metabolism / Q000502:physiology; D006224:Cricetinae; D049452:Green Fluorescent Proteins; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000209:etiology* / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008164:Luminescent Proteins; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D019680:Trinucleotide Repeat Expansion; D014981:Xenopus
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D007473:Ion Channels; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; C097188:polyglutamine