Pressure-induced depression of synaptic transmission in the cerebellar parallel fibre synapse involves suppression of presynaptic N-type Ca2+ channels

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Abstract

High pressure induces CNS hyperexcitability while markedly depressing synaptic transmitter release. We studied the effect of pressure (up to 10.1 MPa) on the parallel fibre (PF) synaptic response in biplanar cerebellar slices of adult guinea pigs. Pressure mildly reduced the PF volley amplitude and to a greater extent depressed the excitatory field postsynaptic potential (fPSP). The depression of the PF volley was noted even at supramaximal stimulus intensities, indicating an effect of pressure on the amplitude of the action potential in each axon. Low concentrations of TTX mimicked the effects of pressure on the PF volley without affecting the fPSP. Application ω-conotoxin GVIA (ω-CgTx) reduced the synaptic efficacy by 34.3 ± 2.7%. However, in the presence of ω-CgTx the synaptic depression at pressure was significantly reduced. Reduced Ca2+ entry by application of Cd2+ or low [Ca2+](o) did not have a similar influence on the effects of pressure. Application of ω-AGA IVA, ω-AGA TK and Funnel-web spider toxin did not affect the synaptic response in concentrations that usually block P-type Ca2+ channels, whilst the N/P/Q-type blocker ω-conotoxin MVIIC reduced the response to 52.7 ± 5.0% indicating the involvement of Q-type channels and R-type channels in the non-N-type fraction of Ca2+ entry. The results demonstrate that N-type Ca2+ channels play a crucial role in the induction of PF synaptic depression at pressure. This finding suggests a coherent mechanism for the induction of CNS hyperexcitability at pressure.

Original languageEnglish
Pages (from-to)4007-4016
Number of pages10
JournalEuropean Journal of Neuroscience
Volume12
Issue number11
DOIs
StatePublished - 25 Nov 2000

Keywords

  • Biplanar slice
  • Cerebellum
  • Guinea pig
  • HPNS
  • Synaptic transmission

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