Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin 1.

@article{Bubien2004CationSA,
  title={Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin 1.},
  author={James K. Bubien and Hong-Long Ji and G. Yancey Gillespie and Catherine M. Fuller and James M. Markert and Timothy B. Mapstone and Dale J. Benos},
  journal={American journal of physiology. Cell physiology},
  year={2004},
  volume={287 5},
  pages={
          C1282-91
        }
}
Psalmotoxin 1 (a component of the venom of a West Indies tarantula) is a 40-amino acid peptide that inhibits cation currents mediated by acid-sensing ion channels (ASIC). In this study we performed electrophysiological experiments to test the hypothesis that Psalmotoxin 1 (PcTX1) inhibits Na+ currents in high-grade human astrocytoma cells (glioblastoma multiforme, or GBM). In whole cell patch-clamped cultured GBM cells, the peptide toxin quickly and reversibly inhibited both inward and outward… 
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Surface Expression of ASIC2 Inhibits the Amiloride-sensitive Current and Migration of Glioma Cells*

The results suggest that the chemical chaperone, glycerol, and the transcriptional regulator, sodium 4-phenylbutyrate, induce the movement of ASIC2 to the plasma membrane, and once there, the basally active inward current characteristic of glioma cells is abolished by inherent negative regulatory mechanisms.

Amiloride-sensitive Na+ channels contribute to regulatory volume increases in human glioma cells.

The ability of the cells to volume regulate subsequent to cell shrinkage by hyperosmolar solutions was abolished by both amiloride and psalmotoxin 1, a member of the Deg/ENaC superfamily of cation channels.

Characterization of the Interaction Between ASIC and BK Channels in Glioma Derived Cell Lines

High grade glioma display a heterogeneous outward current profile and BK channels comprise a large part of the current but, unlike primary cultures of glial cells, are no longer regulated by changes in extracellular pH.

Knockdown of ASIC1 and Epithelial Sodium Channel Subunits Inhibits Glioblastoma Whole Cell Current and Cell Migration*

Interactions between ASIC1, α ENaC, and γENaC are shown, consistent with these subunits interacting with each other to form an ion channel in glioma cells.

Interaction of ASIC and BK Channels in Human Glioma and its Role in cell Migration and Proliferation

The data suggests a complex mechanism for migration and invasion of gliomas, and evidence supporting the null hypothesis for migration of astrocytoma stage III and IV and Invasion decreased in glioblastoma stage IV with the BK inhibitor.

The receptor site of the spider toxin PcTx1 on the proton‐gated cation channel ASIC1a

Results obtained from chimeras indicate that PcTx1 does not bind to ASIC1a transmembrane domains, involved in formation of the ion pore, but binds principally on both cysteine‐rich domains I and II of the extracellular loop.

Two PKC consensus sites on human acid-sensing ion channel 1b differentially regulate its function.

The data suggest that S40 and S499 are critical sites mediating the modulation of hASIC1b by PKC, and differentially regulate hASic1b and mediate the effects of PKC activation or PKC inhibition on hAS IC1b.

Mambalgin-2 Induces Cell Cycle Arrest and Apoptosis in Glioma Cells via Interaction with ASIC1a

Recombinant analog of mambalgin-2 from black mamba Dendroaspis polylepis inhibited amiloride-sensitive currents at ASIC1a both in Xenopus laevis oocytes and in U251 MG cells, while its mutants with impaired activity towards this channel did not.

Glioma-specific Cation Conductance Regulates Migration and Cell Cycle Progression*

The data suggest that a specific cation conductance composed of acid-sensing ion channels and ENaC subunits regulates migration and cell cycle progression in gliomas.

Ion Channels as Therapeutic Targets in High Grade Gliomas

It is proposed that targeting ion channels and repurposing commercially available ion channel inhibitors may hold the key to new therapeutic avenues in high grade gliomas and whether ion channels hold the mechanistic key to the newfound success of electrotherapies.

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