title: Malignant human gliomas express an amiloride-sensitive Na+ conductance.
abstract: Human astrocytoma cells were studied using whole cell patch-clamp recording. An inward, amiloride-sensitive Na+ current was identified in four continuous cell lines originally derived from human glioblastoma cells (CH235, CRT, SKMG-1, and U251-MG) and in three primary cultures of cells obtained from glioblastoma multiforme tumors (up to 4 passages). In addition, cells freshly isolated from a resected medulloblastoma tumor displayed this same characteristic inward current. In contrast, amiloride-sensitive currents were not observed in normal human astrocytes, low-grade astrocytomas, or juvenile pilocytic astrocytomas. The only amiloride-sensitive Na+ channels thus far molecularly identified in brain are the brain Na+ channels (BNaCs). RT-PCR analyses demonstrated the presence of mRNA for either BNaC1 or BNaC2 in these tumors and in normal astrocytes. These results indicate that the functional expression of amiloride-sensitive Na+ currents is a characteristic feature of malignant brain tumor cells and that this pathway may be a potentially useful target for therapeutic intervention.
authors.affiliation: Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Bubien
authors.forename: D A
authors.initials: DA
authors.lastname: Keeton
authors.forename: C M
authors.initials: CM
authors.lastname: Fuller
authors.forename: G Y
authors.initials: GY
authors.lastname: Gillespie
authors.forename: A T
authors.initials: AT
authors.lastname: Reddy
authors.forename: T B
authors.initials: TB
authors.lastname: Mapstone
authors.forename: D J
authors.initials: DJ
authors.lastname: Benos
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D000584:Amiloride