Presynaptic inhibition of excitatory synaptic transmission by muscarinic and metabotropic glutamate receptor activation in the hippocampus: are Ca2+ channels involved?

Neuropharmacology. 1995 Nov;34(11):1549-57. doi: 10.1016/0028-3908(95)00119-q.


Activation of either muscarinic cholinergic or metabotropic glutamatergic presynaptic receptors inhibits evoked excitatory synaptic responses in the hippocampus. We have investigated two possible mechanisms underlying these actions using whole-cell recording from CA3 pyramidal cells in hippocampal slice cultures. Application of either methacholine (MCh, 10 microM) or trans-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD, 10 microM) was found to reduce the frequency of miniature excitatory postsynaptic currents (mEPSCs) by roughly 50%, without changing their mean amplitude. The voltage-dependent Ca2+ channel blocker Cd2+ (100 microM), in contrast, had no effect on the mEPSC frequency. When the extracellular [K+] was increased from 2.7 to 16 mM, the mEPSC frequency increased from 1.7 to 4.9 Hz. This increase could be completely reversed by applying Cd2+, indicating that it was triggered by voltage-dependent Ca2+ influx. MCh and t-ACPD each decreased the mEPSC frequency by roughly 50% under these conditions. Because the agonists were equally effective in inhibiting spontaneous release whether voltage-dependent channels were activated or not, we conclude that presynaptic cholinergic and glutamatergic inhibition is not mediated by inhibition of presynaptic Ca2+ channels, but rather by a direct interference in the neurotransmitter release process at some point subsequent to Ca2+ influx.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / physiology
  • Cycloleucine / analogs & derivatives*
  • Cycloleucine / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Methacholine Chloride / pharmacology*
  • Muscarinic Agonists / pharmacology*
  • Potassium / physiology
  • Rats
  • Receptors, Metabotropic Glutamate / drug effects*
  • Synaptic Transmission / drug effects*


  • Calcium Channels
  • Excitatory Amino Acid Agonists
  • Muscarinic Agonists
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • Methacholine Chloride
  • 1-amino-1,3-dicarboxycyclopentane
  • Potassium