The toxin Tx4(6-1) from the spider Phoneutria nigriventer slows down Na+ current inactivation in insect CNS via binding to receptor site 3

Tx4(6-1) a neurotoxic peptide from the venom of the aggressive South American ‘armed’ spider Phoneutria nigriventer, has been previously isolated and sequenced. It shows no detectable activity in mice but affects the peripheral nervous system of insects by stimulating glutamate release at the neuromuscular junction. Here we investigate possible interactions of the toxin with voltage-activated sodium channels (Nav). We confirm that it is ineffective on mammalian Nav channels, and establish that it competes with the α-like toxin 125I-Bom IV, for binding on the site 3 of insect Nav channel (IC50 value around 25 nM). The physiological consequences of this binding to the insect Nav channel are shown by electrophysiology: Tx4(6-1) prolongs evoked axonal action potentials (APs) (<500 μs duration in control). Prolonged 8–10 ms or ‘plateau’ 500–800 ms APs accompanied by repetitive firing at 80–150 Hz are recorded after 4–8 min of toxin action. This modification of evoked activity is due to a slowing down of sodium current inactivation. Effects of Tx4(6-1) on sodium current are compared with those of a typical scorpion α-toxin and of some other spider toxins active on insect Nav channels. At the end of long voltage pulses, the maintained inward sodium current may represent 50% of the peak current after scorpion α-toxin but only about 8–10% after spider toxins. To understand the slight differences in the effects of α-scorpion and spider toxins on the insect Nav channel, structural studies of toxin–channels interactions would be necessary.