A novel, extremely fast, feedback inhibition of glutamate release in the crayfish neuromuscular junction

Y. M. Kupchik, H. Parnas, I. Parnas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Feedback inhibition serves to modulate release when neurotransmitter levels in the synaptic cleft are elevated. The "classical" feedback auto-inhibition of neurotransmitter release is predominantly mediated by activation of presynaptic G-protein-coupled receptors (GPCRs) and exhibits slow kinetics. In cholinergic and glutamatergic synapses and for focal graded depolarization of the axon terminal, feedback inhibition was found to be voltage-dependent. At high depolarizations, such as the one produced by an action potential, low concentrations of neurotransmitter were insufficient to inhibit release. On the other hand, at higher neurotransmitter concentrations, feedback inhibition was observed also for action potential-evoked release. This finding suggests the presence of an additional mechanism of feedback inhibition that operates also at large presynaptic depolarizations. Using the glutamatergic crayfish neuromuscular junction we discovered a novel, extremely fast, form of feedback inhibition which hampers action potential-evoked release. This novel mechanism is pertussis toxin-insensitive, and is activated already 1 ms after flash photolysis producing glutamate concentrations higher than the ones required to activate the classical feedback inhibition. This finding implies that this mechanism is recruited only when glutamate levels in the synaptic cleft are relatively high (after high-frequency activation or in pathological conditions). We show that both the classical and this novel mechanism operate under physiological conditions.

Original languageAmerican English
Pages (from-to)44-54
Number of pages11
JournalNeuroscience
Volume172
DOIs
StatePublished - 13 Jan 2011

Keywords

  • Feedback inhibition
  • GPCRs
  • Glutamate release
  • MGluRs
  • Neurotransmitter release
  • Presynaptic modulation

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