Modulatory action of metabotropic glutamate receptor (mGluR) 5 on mGluR1 function in striatal cholinergic interneurons.
Within basal ganglia, group I metabotropic glutamate receptor subtypes (mGluR1 and 5) frequently co-localize in the same neuron. However, little is known about how these receptors functionally interact. We addressed this issue by means of electrophysiological recordings of striatal cholinergic interneurons, a neuronal subtype that co-express both group I mGluRs. The group I non-selective agonist 3,5-DHPG induced a membrane depolarization/inward current that was prevented by co-application of LY 367385, a selective mGluR1 antagonist, and SIB 1757 or MPEP, blockers of mGluR5 subtype. The reversal potential for the response to 3,5-DHPG was close to the equilibrium potential for potassium channels. Repeated bath or focal applications of 3,5-DHPG induced a progressive decline in the amplitude of the membrane depolarization, suggesting that group I mGluRs undergo receptor desensitization. Interestingly, in the presence of the mGluR5 blocker, SIB 1757, this event was not observed, whereas it occurred in LY 367385. PKC blockers chelerythrine and calphostin C mimicked the inhibitory effect of SIB 1757. In a subset of interneurons, in MPEP or SIB 1757, 3,5-DHPG induced a 0.5-1 Hz oscillatory response, that was prevented by L-type Ca2+ channel blockers, and by the tyrosine kinase inhibitors genistein and lavendustin. Together, these data suggest that mGluR5 modulates mGluR1 activity to shape cell excitability.
Bonsi
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Laboratorio di Neurofisiologia, Fondazione Santa Lucia, C.E.R.C., Rome, Italy.
Cuomo
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De Persis
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C
Centonze
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Bernardi
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Calabresi
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Pisani
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A
D000109:Acetylcholine / Q000378:metabolism*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009553:Nimodipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D013779:Tetrodotoxin; D009553:Nimodipine; D000109:Acetylcholine