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

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Abstract
The interactions between .alpha.-latrotoxin (.alpha.-LTx), a neurosecretagogue purified from the venom of the black widow spider, and the trivalent cations Al3+, Y3+, La3+, Gd3+, and Yb3+ were investigated in rat striatal synaptosomal preparations. All trivalent cations tested were inhibitors of .alpha.-LTx-induced [3H]dopamine ([3H]DA) release (order of potency: Yb3+ > Gd3+ .apprxeq. Y3+ > La3+ > Al3+). Only with Al3+ could inhibition of [3H]DA release be attributed to a block of 125I-.alpha.-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 .alpha.-LTx-induced [3H]DA release at times when .alpha.-LTx-stimulated release was already evident. .alpha.-LTx-induced synaptosomal membrane depolarization was blocked by La3+, but not affected by Gd3+, Y3+, and Yb3+. .alpha.-LTx-stimulated uptake of 45Ca2+ was inhibited by all trivalent cations tested. These results demonstrate that there exist at least three means by which trivalent cations can inhibit .alpha.-LTx action in rat striatal synaptosomal prepartions: (1) inhibition of .alpha.-LTx binding (Al3+); (2) inhibition of .alpha.-LTx-induced depolarization (La3+); and (3) inhibition of .alpha.-LTx-induced 45Ca2+ uptake (Gd3+, Y3+, Yb3+, La3+).

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