Metabotropic glutamate receptors 1 and 5 differentially regulate bulbar dopaminergic cell function.
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.
Jian
Kuihuan
K
Dipartimento di Biologia ed Evoluzione, Università di Ferrara, Sez Fisiologia e Biofisica, Via Borsari 46, 44100 Ferrara, Italy.
Cifelli
Pierangelo
P
Pignatelli
Angela
A
Frigato
Elena
E
Belluzzi
Ottorino
O
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
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