{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:08:03Z","timestamp":1791104883865,"version":"4.1.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1999,10,1]]},"abstract":"<jats:p>Metabotropic glutamate receptors modulate neuronal excitability via a multitude of mechanisms, and they have been implicated in the pathogenesis of neurodegenerative processes. Here we investigated the responses mediated by group I metabotropic glutamate receptors (mGluRs) in dopamine neurons of the rat substantia nigra pars compacta, using whole cell patch-clamp recordings in combination with microfluorometric measurements of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and [Na<jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>. The selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (3,5-DHPG) was bath-applied (20 \u03bcM, 30 s to 2 min) or applied locally by means of short-lasting (2\u20134 s) pressure pulses, delivered through an agonist-containing pipette positioned close to the cell body of the neuron. 3,5-DHPG evoked an inward current characterized by a transient and a sustained component, the latter of which was uncovered only with long-lasting agonist applications. The fast component coincided with a transient elevation of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, whereas the total current was associated with a rise in [Na<jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>. These responses were not affected either by the superfusion of ionotropic excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and d-2-amino-5-phosphono-pentanoic acid (d-APV), nor by the sodium channel blocker tetrodotoxin (TTX). (S)-\u03b1-methyl-4-carboxyphenylglycine (S-MCPG) and the more selective mGluR1 antagonist 7(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate (CPCCOEt) depressed both 3,5-DHPG\u2013induced inward current components and, although less effectively, the associated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>elevations. On repeated agonist applications the inward current and the calcium transients both desensitized. The time constant of recovery from desensitization differed significantly between these two responses, being 67.4 \u00b1 4.4 s for the inward current and 28.6 \u00b1 2.7 s for the calcium response. Bathing the tissue in a calcium-free\/EGTA medium or adding thapsigargin (1 \u03bcM) to the extracellular medium prevented the generation of the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>transient, but did not prevent the activation of the inward current. These electrophysiological and fluorometric results show that the 3,5-DHPG\u2013induced inward current and the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>elevations are mediated by independent pathways downstream the activation of mGluR1.<\/jats:p>","DOI":"10.1152\/jn.1999.82.4.1974","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T05:25:37Z","timestamp":1514179537000},"page":"1974-1981","source":"Crossref","is-referenced-by-count":59,"title":["Group I Metabotropic Glutamate Receptors Mediate an Inward Current in Rat Substantia Nigra Dopamine Neurons That Is Independent From Calcium Mobilization"],"prefix":"10.1152","volume":"82","author":[{"given":"Ezia","family":"Guatteo","sequence":"first","affiliation":[{"name":"IRCCS S. Lucia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola B.","family":"Mercuri","sequence":"additional","affiliation":[{"name":"IRCCS S. 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