FTX-3

A polyamine component of Agelenopsis aperta spider venom designated FTX is reported to be a selective antagonist of P-type calcium channels in the mammalian brain.Consequently, this component has frequently been used as a pharmacol. tool to determine the presence, distribution, and function of P-type channels in physiol. systems.We describe antagonism of calcium channels by the synthesized polyamine FTX-3.3, which has the proposed structure of natural FTX.We also examined a corresponding polyamine amide, sFTX-3.3.These polyamines are critically evaluated for antagonism of three high-threshold calcium channel subtypes in rat neurons through the use of the whole-cell patch-clamp technique.FTX-3.3 (IC₅₀ = ∼0.13 mM) is approx. twice as potent as sFTX-3.3 (IC₅₀ = ∼0.24 mM) against P-type channels and ∼3-fold more potent against N-type channels (FTX-3.3, IC₅₀ = ∼0.24 mM; sFTX-3.3, IC35₀ = ∼0.70 mM).Both polyamines also block L-type calcium channels with similar potencies.SFTX-3.3 (1 mM) and FTX-3.3 (0.5 mM) typically block 505 and 65% of BAy K8644-enhanced L-type current, resp.Antagonism of each calcium channel subtype is voltage dependent, with less inhibition of Ba²⁺ currents at more-pos. potentials.These data show that both sFTX-3.3 and FTX-3.3 antagonize P-, N-, and L-type calcium channels in mammalian Purkinje and superior cervical ganglia neurons with similar IC₅₀ values.