Two types of scorpion receptor sites, one related to the activation, the other to the inactivation of the action potential sodium channel.

The action of the neurotoxin in Buthinae scorpion venoms (Androctonus, Buthus or Leiurus genera) has been extensively studied. These proteins induce a prolongation of the action potential of nerves and muscles by slowing down inactivation of the sodium channel. Their affinity for their receptor site depends on membrane potential. In the present report we describe a toxin from a Centrurinae scorpion, Centruroides suffusus, which binds rat brain synaptosomes at a receptor site distinct from the Buthinae scorpion site independently of voltage. We name Androctonus-like toxins, alpha-scorpion toxins (alpha-ScTX), and Centruroides-like toxins, beta-scorpion toxins (beta-ScTX). We further report that beta-ScTX induces repetitive firing in frog myelinated nerve fibres by producing an abnormal sodium permeability. The beta-toxin binds specifically to rat brain synaptosomes (Kd = 3 nM) and induces an inhibition of the uptake and a stimulation of the release of GABA at concentrations which are in good agreement with the Kd value. These effects are blocked by tetrodotoxin. The binding site of beta -ScTX is distinct from those of other neurotoxins acting on the sodium channel like tetrodotoxin, alpha-ScTX and veratridine. The alpha-ScTX/beta-ScTX binding site capacities decreases as development of rat brain synaptosomes progresses ; at day 7 after birth, it is 1.1. and at day 39, 0.3.