Marco Capogna

Presynaptic inhibition of calcium-dependent and -independent release elicited with ionomycin, gadolinium, and alpha-latrotoxin in the hippocampus

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1. Presynaptic inhibition of synaptic transmission in the hippocampus was investigated by comparing the effects of several agonists on miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs). 2. The Ca2+ ionophore ionomycin increased the frequency of mEPSCs and mIPSCs but did not affect their amplitude. Ionomycin-induced release required extracellular Ca2+ and was prevented by pretreatment with botulinum neurotoxin serotype F, like evoked synaptic transmission. Unlike evoked transmission, however, this increase did not involve activation of voltage-dependent Ca2+ channels because it was insensitive to Cd2+. 3. Both the lanthanide gadolinium and alpha-latrotoxin produced increases in the frequency of mEPSCs and mIPSCs, but their actions were independent of extracellular Ca2+. 4. Adenosine, the gamma-aminobutyric acid-B (GABAB) receptor agonist baclofen, and a mu-opioid receptor agonist strongly reduced the frequency of synaptic currents triggered by all three secretagogues. 5. We conclude that activation of these presynaptic receptors can reduce high frequencies of vesicular glutamate and GABA release by directly impairing transmitter exocytosis. Presynaptic inhibition of gadolinium- and alpha-latrotoxin-induced release indicates that this impairment occurs without changes in intraterminal Ca2+ homeostasis and when vesicle fusion is rendered Ca2+ independent, respectively. 6. The inhibition of ionomycin-induced release provides additional evidence for a direct, neurotransmitter receptor-mediated modulation of the proteins underlying vesicular docking or fusion as an important component of presynaptic inhibition of evoked synaptic transmission.

Original languageEnglish
JournalJournal of Neurophysiology
Volume75
Issue5
Pages (from-to)2017-28
Number of pages12
ISSN0022-3077
DOIs
Publication statusPublished - May 1996
Externally publishedYes

    Research areas

  • Adenosine/pharmacology, Animals, Baclofen/pharmacology, Botulinum Toxins/pharmacology, Calcium/physiology, Calcium Channels/drug effects, Cardiovascular Agents/pharmacology, D-Ala(2),MePhe(4),Met(0)-ol-enkephalin/pharmacology, Depression, Chemical, Extracellular Space/drug effects, GABA Agonists/pharmacology, Gadolinium/pharmacology, Hippocampus/drug effects, In Vitro Techniques, Ionomycin/pharmacology, Ionophores/pharmacology, Neurotransmitter Agents/metabolism, Patch-Clamp Techniques, Rats, Receptors, Presynaptic/agonists, Spider Venoms/pharmacology, Synaptic Transmission/drug effects

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