2 COMPONENTS OF METABOTROPIC GLUTAMATE RESPONSES IN ACUTELY DISSOCIATED CA3 PYRAMIDAL NEURONS OF THE RAT

Citation
N. Harata et al., 2 COMPONENTS OF METABOTROPIC GLUTAMATE RESPONSES IN ACUTELY DISSOCIATED CA3 PYRAMIDAL NEURONS OF THE RAT, Brain research, 711(1-2), 1996, pp. 223-233
Citations number
52
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
00068993
Volume
711
Issue
1-2
Year of publication
1996
Pages
223 - 233
Database
ISI
SICI code
0006-8993(1996)711:1-2<223:2COMGR>2.0.ZU;2-C
Abstract
The excitatory and inhibitory actions of metabotropic glutamate recept or (mGluR) agonists were investigated in acutely dissociated rat hippo campal CA3 pyramidal neurons, using the conventional whole-cell and ny statin-perforated patch recording configurations under the voltage-cla mp condition. With the conventional whole-cell recording, glutamate (G lu) and quisqualic acid (QA) induced only ionotropic inward currents a ccompanied by increased membrane conductance at a holding potential (V -H) of -45 mV. The response was reversibly blocked in the presence of D-2-amino-5-phosphonopentanoic acid (D-AP5) and 6-cyano-7-nitroquinoxa line-2,3-dione (CNQX), the antagonists of N-methyl-D-aspartate (NMDA) receptor and non-NMDA receptor, respectively. With nystatin-perforated patch recording, mGlu responses insensitive to both D-AP5 and CNQX we re observed. Fifty-five % of the cells responded by a slow inward curr ent accompanied by conductance decrease (I-mGlui) at a V-H of -44 mV. One % of the neurons showed an outward current with conductance increa se (I-mGluo), and 34% of the neurons showed I-mGluo followed by I-mGlu i. The onset of I-mGluo occurred approximately 900 ms after the respon se to 30 mM K+. The time to peak of I-mGluo were 32- to 79-times longe r than those of ionotropic responses. I-mGlui appeared at lower concen trations than ionotropic Glu responses, whereas I-mGluo appeared at si milar concentrations as ionotropic responses. The rank order of affini ty was QA > Glu >(+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (tACPD) for both I-mGlui and I-mGluo. Half-maximal effective concentr ations (EC(50)) and the threshold concentrations for the three agonist s were four- to tenfold lower for I-mGlui than for I-mGluo. The curren t-voltage relationship showed that the reversal potentials of I-mGlui and I-mGluo shifted 55 and 59 mV, respectively, for a tenfold change i n extracellular K+ concentration, indicating that K+ is the charge car rier of both mGlu responses. During I-mGlui, both the leakage current and muscarine-sensitive voltage-dependent K+ current (M current) were suppressed. I-mGluo induced by 10(-4) M tACPD was abolished by 3 . 10( -7) M charybdotoxin and 10(-6) M ryanodine. These results show that th ere are two components of mGlu responses in CA3 pyramidal neurons and that I-mGlui and I-mGluo show different pharmacological properties.