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

被引:33
作者
Bubien, JK
Ji, HL
Gillespie, GY
Fuller, CM
Markert, JM
Mapstone, TB
Benos, DJ
机构
[1] Univ Alabama Birmingham, Dept Physiol & Biophys, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Dept Surg, Div Neurosurg, Birmingham, AL 35294 USA
[3] Emory Univ, Dept Neurosurg, Atlanta, GA 30322 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2004年 / 287卷 / 05期
关键词
patch clamp; amiloride; ion channels; acid-sensing ion channels;
D O I
10.1152/ajpcell.00077.2004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:C1282 / C1291
页数:10
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