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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

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

¹Department of Physiology and Biophysics, and ²Department of Surgery, Division of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ³Department of Neurosurgery, Emory University, Atlanta, Georgia 30322

Submitted 9 February 2004 ; accepted in final form 6 July 2004

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.

patch clamp; amiloride; ion channels; acid-sensing ion channels

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