beta-Agkistrodotoxin inhibition of Ca2+-dependent release of glutamate, aspartate, glycine and gamma-aminobutyric acid from cerebrocortical synaptosomes following its binding to synaptic membrane

Abstract

The binding properties of beta-AgTX, a snake pre-synaptic toxin, membranes and its effect on transmitter release from cerebrocortical synaptosomes were investigated. Assay of [125I]-beta-AgTX binding to rat synaptic membrane revealed a high affinity binding site for the toxin within the synaptic membrane. Preincubation with beta-AgTX inhibited K+-evoked Ca2+-dependent glutamate release from synaptosomes in a concentration-dependent manner, as determined by an on-line enzyme-linked fluorometric assay. The toxin also blocked the Ca2+-dependent release of other transmitters, aspartate, glycine, and GABA induced by K+-depolarization. However, Ca2+-ionophore, ionomycin-stimulated Ca2+-dependent transmitter release was not significantly affected by beta-AgTX, indicating that the toxin inhibits transmitter release by reducing the entry of Ca2+ into cytoplasm. It is suggested that beta-AgTX-binding site in synaptic membrane is related to the release of a variety of transmitters.