title: Metabotropic glutamate receptors 1 and 5 differentially regulate bulbar dopaminergic cell function.
abstract: Effects of activation of metabotropic glutamatergic receptors (mGluR) were investigated in mouse dopaminergic olfactory bulb neurons. After blockage of ionotropic receptors, focal application of glutamate or of group I/II mGluR agonist t-ACPD resulted in a depolarization, paralleled by an inward current in voltage-clamp conditions. The Group I agonist DHPG induced a depolarization, which could be largely blocked by mGluR1 antagonists. The DHPG action i) was prevented by buffering intracellular Ca(2+) with BAPTA and by a phospholipase C inhibitor; ii) was not affected by the block of Ca(2+) entry, and iii) was blocked by inhibitors of the Na(+)/Ca(2+) exchanger. These observations were interpreted as a mGluR1-mediated intracellular Ca(2+) release, followed by the activation of an electrogenic Na(+)/Ca(2+) exchanger. The mGluR5 agonist CHPG induced a hyperpolarization of membrane potential, resulting in a decrease of the spontaneous firing frequency. CHPG induced i) a decrease in membrane resistance; ii) an increase in the action potential repolarization rate, and iii) an increase in the amplitude of the afterhyperpolarization. This was interpreted as a mGluR5-mediated opening of a K(+) conductance. These data suggest that mGluR1 and mGluR5 play different and non-overlapping roles in the regulation of the excitability of bulbar dopaminergic neurons.
authors.affiliation: Dipartimento di Biologia ed Evoluzione, Università di Ferrara, Sez Fisiologia e Biofisica, Via Borsari 46, 44100 Ferrara, Italy.
authors.forename: Kuihuan
authors.initials: K
authors.lastname: Jian
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Cifelli
authors.forename: Angela
authors.initials: A
authors.lastname: Pignatelli
authors.forename: Elena
authors.initials: E
authors.lastname: Frigato
authors.forename: Ottorino
authors.initials: O
authors.lastname: Belluzzi
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010648:Phenylacetates / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C107349:2-chloro-5-hydroxyphenylglycine; D010648:Phenylacetates; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D004533:Egtazic Acid; D010738:Type C Phospholipases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D005998:Glycine; D004298:Dopamine