Marco Capogna

Calcium-independent actions of alpha-latrotoxin on spontaneous and evoked synaptic transmission in the hippocampus

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1. The black widow spider venom component, alpha-latrotoxin (alpha-LTx) (< 0.5 nM), increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in hippocampal CA3 pyramidal cells 14-fold, without changing their amplitude. 2. This action of alpha-LTx was not affected by application of Ca(2+)-free/ethylene glycol-bis(b-aminoethyl ether)-N,N,N',N'-tetraacetic acid-containing saline, 100 microM Cd2+, or 50 microM Gd3+. The increase in mEPSC frequency was thus not due to an influx of Ca2+ into the axon terminal via voltage-dependent Ca2+ channels or alpha-LTx-induced pores. 3. alpha-LTx did not increase spontaneous release when synaptic transmission had been impaired by botulinum toxin/F. 4. alpha-LTx reduced the amplitude of EPSCs, elicited with stimulation of mossy fibers, without affecting paired-pulse facilitation. 5. The Ca2+ ionophore ionomycin (2-2.5 microM) also enhanced the frequency of mEPSCs, but unlike alpha-LTx, potentiated evoked EPSCs and reduced paired-pulse facilitation. Application of N-methyl-D-aspartate elicited a high frequency of Ca(2+)-dependent, tetrodotoxin-sensitive spontaneous EPSCs, but did not affect evoked EPSC amplitude. Agents that stimulate vesicular release by increasing presynaptic Ca2+ influx thus do not mimic the alpha-LTx-induced depression of evoked EPSCs. 6. We conclude that entry of Ca2+ into presynaptic axon terminals is not responsible for the effects of low concentrations of alpha-LTx on either spontaneous or evoked transmitter release in the hippocampus. 7. Potential presynaptic mechanisms that could mediate the opposing actions of alpha-LTx on spontaneous and evoked transmitter release in the hippocampus (i.e., alpha-LTx-induced ionic pores, depletion of synaptic vesicles, actions on exocytotic proteins) are discussed.

Original languageEnglish
JournalJournal of Neurophysiology
Volume76
Issue5
Pages (from-to)3149-58
Number of pages10
ISSN0022-3077
DOIs
Publication statusPublished - Nov 1996
Externally publishedYes

    Research areas

  • Animals, Calcium/pharmacology, Evoked Potentials/drug effects, Hippocampus/drug effects, Rats, Spider Venoms/pharmacology, Synaptic Transmission/drug effects

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