title: Presynaptic inhibition of excitatory synaptic transmission by muscarinic and metabotropic glutamate receptor activation in the hippocampus: are Ca2+ channels involved?
abstract: 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.
authors.affiliation: Brain Research Institute, University of Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Scanziani
authors.forename: B H
authors.initials: BH
authors.lastname: Gahwiler
authors.forename: S M
authors.initials: SM
authors.lastname: Thompson
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D016210:Methacholine Chloride / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D015220:Calcium Channels; D018690:Excitatory Amino Acid Agonists; D018721:Muscarinic Agonists; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; D016210:Methacholine Chloride; C036361:1-amino-1,3-dicarboxycyclopentane; D011188:Potassium