Am J Physiol Cell Physiol AJP: Gastrointestinal and Liver Physiology
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Am J Physiol Cell Physiol (July 14, 2004). doi:10.1152/ajpcell.00077.2004
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Submitted on February 9, 2004
Accepted on July 6, 2004

Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin1

James K Bubien1*, Hong-Long Ji1, G. Y Gillespie2, Catherine M Fuller1, James M Markert2, Timothy B Mapstone3, and Dale J Benos1

1 Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL, USA
2 Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
3 Neurosurgery, Emory University, Atlanta, GA, USA

* To whom correspondence should be addressed. E-mail: bubien{at}uab.edu.

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 U215-MG). The selectivity sequence yielded a unique biophysical fingerprint with inward potassium conductance approximately 4-fold greater than sodium, lithium, and calcium. These observations suggest that PcTX1 may prove useful in determining whether or not 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.




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