%0 Journal Article %A Luciene B. Vieira %A Christopher Kushmerick %A Michael E. Hildebrand %A Esperanza Garcia %A Antony Stea %A Marta N. Cordeiro %A Michael Richardson %A Marcus Vinicius Gomez %A Terrance P. Snutch %T Inhibition of High Voltage-Activated Calcium Channels by Spider Toxin PnTx3-6 %D 2005 %R 10.1124/jpet.105.087023 %J Journal of Pharmacology and Experimental Therapeutics %P 1370-1377 %V 314 %N 3 %X Animal peptide toxins have become powerful tools to study structure-function relationships and physiological roles of voltage-activated Ca2+ 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 Ca2+ channels expressed in human embryonic kidney 293 cells and endogenous Ca2+ channels in N18 neuroblastoma cells. Whole-cell patch-clamp measurements indicate that PnTx3-6 reversibly inhibited L-(α1C/Cav1.2), N-(α1B/Cav2.2), P/Q-(α1A/Cav2.1), and R-(α1E/Cav2.3) type channels with varying potency (α1B > α1E > α1A > α1C) and IC50 values of 122, 136, 263, and 607 nM, respectively. Inhibition occurred without alteration of the kinetics or the voltage dependence of the exogenously expressed Ca2+ 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 Ca2+ channels subtypes, application of 1 μM PnTx3-6 did not affect α1G/Cav3.1 T-type Ca2+ channels. Based on our study, we suggest that PnTx3-6 acts as a ω-toxin that targets high voltage-activated Ca2+ channels, with a preference for the Cav2 subfamily (N-, P/Q-, and R-types). The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/314/3/1370.full.pdf