Cn11, the first example of a scorpion toxin that is a true blocker of Na(+) currents in crayfish neurons.

Abstract

A novel crustacean toxin (Cn11) was isolated and characterized from the venom of the Mexican scorpion Centruroides noxius Hoffmann. It contains 63 amino acid residues and is stabilized by four disulphide bridges. It is lethal to crustaceans (Cambarellus montezumae), less toxic to insects (crickets) and non-toxic to mammals (mice) at the doses assayed. In neurons isolated from the X organ-sinus gland system of the crayfish Procambarus clarkii, it blocks the Na(+) currents with an estimated K(m) of 320 nmol l(-1), without affecting the Ca(2+) and K(+) currents. The voltage-gated tetrodotoxin-sensitive Na(+) current was recorded from X organ neurons in culture 24 h after plating using the whole-cell clamp configuration. The Na(+) current was isolated by blocking Ca(2+) currents with Cd(2+) and Cs(+) and K(+) currents with tetraethylammonium and 4-aminopyridine. Under control conditions, the Na(+) currents were activated at -40 mV with a maximum amplitude at 0 mV. In the presence of 1 micromol l(-1) Cn11, the Na(+) current amplitude was reduced by 75 % without apparent modifications to the gating mechanism. These findings suggest that Cn11 selectively blocks a Na(+) channel. It is the first representative of a new group of scorpion toxins specific for this molecular target.