• Luciene B Vieira, Christopher Kushmerick, Michael E Hildebrand, Esperanza Garcia, Antony Stea, Marta N Cordeiro, Michael Richardson, Marcus Vinicius Gomez, and Terrance P Snutch.
• Biotechnology Laboratory, University of British Columbia, Vancouver, Canada.
• J. Pharmacol. Exp. Ther. 2005 Sep 1; 314 (3): 1370-7.

AbstractAnimal peptide toxins have become powerful tools to study structure-function relationships and physiological roles of voltage-activated Ca(2+) channels. In the present study, we investigated the effects of PnTx3-6, a neurotoxin purified from the venom of the spider Phoneutria nigriventer on cloned mammalian Ca(2+) channels expressed in human embryonic kidney 293 cells and endogenous Ca(2+) channels in N18 neuroblastoma cells. Whole-cell patch-clamp measurements indicate that PnTx3-6 reversibly inhibited L-(alpha(1C)/Ca(v)1.2), N-(alpha(1B)/Ca(v)2.2), P/Q-(alpha(1A)/Ca(v)2.1), and R-(alpha(1E)/Ca(v)2.3) type channels with varying potency (alpha(1B) > alpha(1E) > alpha(1A) > alpha(1C)) and IC(50) values of 122, 136, 263, and 607 nM, respectively. Inhibition occurred without alteration of the kinetics or the voltage dependence of the exogenously expressed Ca(2+) channels. In N18 cells, PnTx3-6 exhibited highest potency against N-type (conotoxin-GVIA-sensitive) current. In contrast to its effects on high voltage-activated Ca(2+) channels subtypes, application of 1 microM PnTx3-6 did not affect alpha(1G)/Ca(v)3.1 T-type Ca(2+) channels. Based on our study, we suggest that PnTx3-6 acts as a omega-toxin that targets high voltage-activated Ca(2+) channels, with a preference for the Ca(v)2 subfamily (N-, P/Q-, and R-types).

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