Metabotropic glutamate receptors modulate neuronal excitabil- ity via a multitude of mechanisms, and they have been implicated in the pathogenesis of neurodegenerative processes. Here we investi- gated 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 combina- tion with microfluorometric measurements of [Ca2 ]i and [Na ]i. The selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (3,5-DHPG) was bath-applied (20 M, 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 un- covered only with long-lasting agonist applications. The fast compo- nent coincided with a transient elevation of [Ca2 ]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)- -methyl-4-carboxyphenyl- glycine (S-MCPG) and the more selective mGluR1 antagonist 7(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate (CPCCOEt) de- pressed both 3,5-DHPG–induced inward current components and, al- though less effectively, the associated [Ca2 ]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 M) to the extracellular medium prevented the generation of the [Ca2 ]i tran- sient, 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 [Ca2 ]i elevations are mediated by independent pathways downstream the activation of mGluR1.
|Titolo:||Group I metabotropic glutamate receptors mediate an inward current in rat substantia nigra dopamine neurons that is independent from calcium mobilization|
|Data di pubblicazione:||1999|
|Appare nelle tipologie:||1.1 Articolo in rivista|