title: Suppression of presynaptic calcium influx by metabotropic glutamate receptor agonists in neonatal rat hippocampus.
abstract: Mechanisms of presynaptic inhibition by metabotropic glutamate receptor (mGluR) agonists were investigated in neonatal rat hippocampal CA1 region using the optical recording technique recently developed. Following selective loading of presynaptic terminals with a fluorescent Ca2+ indicator dye rhod-2 AM, changes in Ca2+ signals and the corresponding field excitatory postsynaptic potentials (EPSPs) induced by single electrical stimuli to the Schaffer collateral-commissural (SCC) pathway were recorded simultaneously. Application of a mGluR agonist, 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 100 microM) or (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 100 microM), reversibly reduced both the field EPSP and the presynaptic Ca2+ transient, and the quantitative relationship between them was quite similar to that observed during application of Cd2+, a non-selective Ca2+ channel blocker, or in a Ca(2+)-free solution. Application of 4-aminopyridine (4-AP; 1 mM), a blocker of certain subtypes of voltage-dependent K+ channels, significantly inhibited the 1S,3R-ACPD effect. Application of DCG-IV, a novel mGluR2/mGluR3-selective agonist, suppressed field EPSPs only slightly even at a high dose (3 microM). These results suggest that activation of presynaptic mGluR different from mGluR2/mGluR3 suppresses the action potential-triggered Ca2+ influx, probably via 4-AP-sensitive mechanisms, and thereby reduces glutamate release in neonatal rat hippocampal CA1 region.
authors.affiliation: Department of Physiology, Faculty of Medicine, Kanazawa University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yoshino
authors.forename: H
authors.initials: H
authors.lastname: Kamiya
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D003521:Cyclopropanes / Q000494:pharmacology; D003864:Depression, Chemical; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006575:Heterocyclic Compounds, 3-Ring; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D006575:Heterocyclic Compounds, 3-Ring; D018094:Receptors, Metabotropic Glutamate; C068483:rhod-2; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D002118:Calcium; D005998:Glycine