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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-11-5
pubmed:abstractText
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(2+)](i) and [Na(+)](i). The selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (3,5-DHPG) was bath-applied (20 microM, 30 s to 2 min) or applied locally by means of short-lasting (2-4 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(2+)](i), whereas the total current was associated with a rise in [Na(+)](i). 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)-alpha-methyl-4-carboxyphenylglycine (S-MCPG) and the more selective mGluR1 antagonist 7(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate (CPCCOEt) depressed both 3,5-DHPG-induced inward current components and, although less effectively, the associated [Ca(2+)](i) 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+/-4.4 s for the inward current and 28.6+/-2.7 s for the calcium response. Bathing the tissue in a calcium-free/EGTA medium or adding thapsigargin (1 microM) to the extracellular medium prevented the generation of the [Ca(2+)](i) transient, but did not prevent the activation of the inward current. These electrophysiological and fluorometric results show that the 3, 5-DHPG-induced inward current and the [Ca(2+)](i) elevations are mediated by independent pathways downstream the activation of mGluR1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1-amino-1,3-dicarboxycyclopentane, http://linkedlifedata.com/resource/pubmed/chemical/2-Amino-5-phosphonovalerate, http://linkedlifedata.com/resource/pubmed/chemical/3,5-dihydroxyphenylglycine, http://linkedlifedata.com/resource/pubmed/chemical/6-Cyano-7-nitroquinoxaline-2,3-dione, http://linkedlifedata.com/resource/pubmed/chemical/7-(hydroxyimino)cyclopropan(b)chrome..., http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Chromones, http://linkedlifedata.com/resource/pubmed/chemical/Cycloleucine, http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Glycine, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Metabotropic Glutamate, http://linkedlifedata.com/resource/pubmed/chemical/Resorcinols, http://linkedlifedata.com/resource/pubmed/chemical/Tetrodotoxin, http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin, http://linkedlifedata.com/resource/pubmed/chemical/metabotropic glutamate receptor...
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3077
pubmed:author
pubmed:issnType
Print
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1974-81
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10515987-2-Amino-5-phosphonovalerate, pubmed-meshheading:10515987-6-Cyano-7-nitroquinoxaline-2,3-dione, pubmed-meshheading:10515987-Animals, pubmed-meshheading:10515987-Calcium, pubmed-meshheading:10515987-Chromones, pubmed-meshheading:10515987-Cycloleucine, pubmed-meshheading:10515987-Egtazic Acid, pubmed-meshheading:10515987-Excitatory Amino Acid Antagonists, pubmed-meshheading:10515987-Glycine, pubmed-meshheading:10515987-Microscopy, Fluorescence, pubmed-meshheading:10515987-Neurons, pubmed-meshheading:10515987-Patch-Clamp Techniques, pubmed-meshheading:10515987-Rats, pubmed-meshheading:10515987-Receptors, Metabotropic Glutamate, pubmed-meshheading:10515987-Resorcinols, pubmed-meshheading:10515987-Substantia Nigra, pubmed-meshheading:10515987-Tetrodotoxin, pubmed-meshheading:10515987-Thapsigargin
pubmed:year
1999
pubmed:articleTitle
Group I metabotropic glutamate receptors mediate an inward current in rat substantia nigra dopamine neurons that is independent from calcium mobilization.
pubmed:affiliation
IRCCS S. Lucia, Università di Tor Vergata, 00179 Rome, Italy.
pubmed:publicationType
Journal Article, In Vitro