α‐Latrotoxin Releases Both Vesicular and Cytoplasmic Glutamate from Isolated Nerve Terminals

Abstract

.alpha.-Latrotoxin causes a massive release of endogenous glutamate from guinea-pig cerebrocortical synaptosomes. There appear to be two components to the release. In the first 2 min following addition of 1.3 nM .alpha.-latrotoxin, glutamate release is largely energy dependent. Superimposed upon this release is a more slowly developing but ultimately much more extensive release of cytoplasmic glutamate together with .gamma.-aminobutyric acid and nonvesicular amino acids such as aspartate and .alpha.-aminoisobutyrate. In parallel with this cytoplasmic release there is an extensive depletion of ATP, a massive rise in cytoplasmic free Ca2+ concentration, and a severe restriction of synaptosomal respiratory capacity. The cytoplasmic release is only partially Na+ dependent, eliminating a simple reversal of the plasma membrane acidic amino acid carrier. It is concluded that .alpha.-latrotoxin releases both transmitter and cytoplasmic pools of amino acids in synaptosomes and causes a major disruption of terminal integrity.