Malignant human gliomas express an amiloride-sensitive Na+ conductance.
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.
Bubien
J K
JK
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Keeton
D A
DA
Fuller
C M
CM
Gillespie
G Y
GY
Reddy
A T
AT
Mapstone
T B
TB
Benos
D J
DJ
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
D012333:RNA, Messenger; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D000584:Amiloride