Interactions Between α‐Latrotoxin and Trivalent Cations in Rat Striatal Synaptosomal Preparations

The interactions between α‐latrotoxin (α‐LTx), a neurosecretagogue purified from the venom of the black widow spider, and the trivalent cations Al 3+ , Y 3+ , La 3+ , Gd 3+ , and Yb 3+ were investigated in rat striatal synaptosomal preparations. All trivalent cations tested were inhibitors of α‐LTx‐induced [ 3 H]dopamine ([ 3 H]DA) release (order of potency: Yb 3+ > Gd 3+ ± Y 3+ > La 3+ > Al 3+ ). Only with Al 3+ could inhibition of [ 3 H]DA release be attributed to a block of 125 I‐α‐LTx specific binding to synaptosomal preparations. The inhibitory effect of trivalent ions was reversible provided synaptosomes were washed with buffer containing EDTA. Trivalent ions also inhibited α‐LTx‐induced [ 3 H]DA release at times when α‐LTx‐stimulated release was already evident. α‐LTx‐induced synaptosomal membrane depolarization was blocked by La 3+ , but not affected by Gd 3+ , Y 3+ , and Yb 3+ . α‐LTx‐stimulated uptake of 45 Ca 2+ was inhibited by all trivalent cations tested. These results demonstrate that there exist at least three means by which trivalent cations can inhibit α‐LTx action in rat striatal synaptosomal preparations: (1) inhibition of α‐LTx binding (Al 3+ ); (2) inhibition of α‐LTx‐induced depolarization (La 3+ ); and (3) inhibition of α‐LTx‐induced 45 Ca 2+ uptake (Gd 3+ , Y 3+ , Yb 3+ , La 3+ ).