Modulatory action of metabotropic glutamate receptor (mGluR) 5 on mGluR1 function in striatal cholinergic interneurons

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• 作者：P. Bonsi ; D. Cuomo ; C. De Persis ; D. Centonze ; G. Bernardi ; P. Calabresi ; A. Pisani
• 关键词：Metabotropic glutamate receptors ; Striatum ; Electrophysiology ; Cholinergic interneurons ; Desensitization ; TANs
• 刊名：Neuropharmacology
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：49
• 期：Supplement 1
• 页码：104-113
• 全文大小：425 K

文摘

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.