Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin 1.
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 current with an IC50 of 36 +/- 2 pM. The same inhibition was observed in freshly resected GBM cells. However, when the same experiment was performed on normal human astrocytes, the toxin failed to inhibit the whole cell current. We also determined a cationic selectivity sequence for inward currents in three cultured GBM cell lines (SK-MG-1, U87-MG, and U251-MG). The selectivity sequence yielded a unique biophysical fingerprint with inward K+ conductance approximately fourfold greater than that of Na+, Li+, and Ca2+. These observations suggest that PcTX1 may prove useful in determining whether GBM cells express a specific ASIC-containing ion channel type that can serve as a target for both diagnostic and therapeutic treatments of aggressive malignant gliomas.
Bubien
James K
JK
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. bubien@uab.edu
Ji
Hong-Long
HL
Gillespie
G Yancey
GY
Fuller
Catherine M
CM
Markert
James M
JM
Mapstone
Timothy B
TB
Benos
Dale J
DJ
D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002412:Cations; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008094:Lithium / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology*
D002412:Cations; D007473:Ion Channels; C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; D015222:Sodium Channels; D013111:Spider Venoms; D008094:Lithium; D012964:Sodium; D011188:Potassium; D002118:Calcium