Electrophysiological characterization and molecular identification of the Phoneutria nigriventer peptide toxin PnTx2‐6¹

Abstract

A cDNA with 403 nucleotides encoding the precursor of the toxin PnTx2-6 was cloned and sequenced. Subsequent analysis revealed that the precursor begins with a signal peptide and a glutamate-rich propeptide. The succeeding peptide con¢rmed the reported sequence of PnTx2-6. The puri¢ed toxin exerted complex e¡ects on Na + current of frog skeletal muscle. There was a marked decrease of the inactivation kinetics, and a shift to hyperpolarizing potentials of both the Na + conductance and the steady-state inactivation voltage dependences, along with a reduction of the current amplitude. The concentration dependence of the modi¢ed current suggests a K D of 0.8 W WM for the toxin^channel complex. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Phoneutria nigriventerToxin 1: A Novel, State-Dependent Inhibitor of Neuronal Sodium Channels That Interacts with μ Conotoxin Binding Sites

“…The simplest explanation would be that channels with bound Tx1 become nonfunctional. These properties contrasts with those reported for two P. nigriventer venom peptides shown to target sodium channel site 3 and slow down sodium channel inactivation in frog muscle (PnTx2-6; Matavel et al, 2002) suggest that Tx1 may strongly contribute to lethality in human envenomation.…”

Tarantula Huwentoxin-IV Inhibits Neuronal Sodium Channels by Binding to Receptor Site 4 and Trapping the Domain II Voltage Sensor in the Closed Configuration

“…Steady-state inactivation is another important property of VGSCs that can modulate the excitability of neurons (27), can be modified by scorpion and spider toxins (28), and contributes to the inhibitory action of therapeutic agents such as lidocaine. Therefore we investigated the effect of HWTX-IV on steady-state inactivation of neuronal VGSC isoforms (WT Nav1.2, Nav1.3, and Nav1.7) using a standard two-pulse protocol.…”

Some arachnidan peptides with potential medical application

“…Animal venoms or purified toxins evoke complex effects on ion channels, mainly sodium, potassium and calcium channels (56,66,(122)(123)(124)(125)(126)(127) Spider venoms are composed of distinct proteins, peptides and biologically active molecules, most of them neurotoxins (56). These venoms have been described as potentially useful for future discovery and development of new biologically active molecules with medical application (66,115,116,122).…”

“…Some of these toxins, namely PnTx2-5 and PnTx2-6, share 89% of similarity in their amino acid sequence and have been observed to stimulate relaxation of the corpus cavernosum smooth muscle in rabbits, rats and mice, inducing penile erection (54,115,116,121,130,131). Both toxins were described as site-3 toxins, according to their effects on sodium channels (125,132). As observed for scorpion toxins, priapism induced by these toxins has been directly associated with the nitric oxide pathway in rats and mice and this effect has been inhibited by L-NAME (115,116,131).…”