Mechanism of GABAB receptor‐mediated inhibition of spontaneous GABA release onto cerebellar Purkinje cells
Identifieur interne : 000983 ( Main/Exploration ); précédent : 000982; suivant : 000984Mechanism of GABAB receptor‐mediated inhibition of spontaneous GABA release onto cerebellar Purkinje cells
Auteurs : Victoria L. Harvey [Royaume-Uni] ; Gary J. Stephens [Royaume-Uni]Source :
- European Journal of Neuroscience [ 0953-816X ] ; 2004-08.
English descriptors
Abstract
γ‐Aminobutyric acid (GABA)B receptor‐mediated modulation of spontaneous GABA release onto Purkinje cells was investigated in cerebellar slices from 3‐ to 5‐week‐old mice. The GABAB receptor agonists baclofen and CGP 44533 each reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs), with no significant effect on mIPSC amplitude; together, consistent with a presynaptic site of action. The GABAB receptor antagonist CGP 55845 blocked baclofen‐induced inhibition. The sulphydryl alkylating agent N‐ethylmaleimide occluded baclofen effects, implicating Gi/o subunits in mediating a GABAB G protein‐coupled receptor pathway. Baclofen‐induced inhibition persisted in the presence of Ba2+, a blocker of K+ channels, and Cd2+, a blocker of Ca2+ channel‐mediated GABA release. Application of nominally Ca2+‐free extracellular solutions reduced mIPSC frequency and amplitude; however, baclofen produced a significant inhibition in mIPSC frequency, further suggesting that this pathway was independent of Ca2+ influx. Spontaneous GABA release was increased by the adenylate cyclase activator, forskolin, and the phorbol ester, phorbol 12,13‐dibutyrate. However, baclofen‐induced inhibition was not significantly changed in either condition. Baclofen action was also not affected by the adenylate cyclase inhibitor SQ 22536 or the protein kinase C inhibitor chelerythrine chloride. Baclofen still reduced mIPSC frequency in the presence of the polyvalent cation ruthenium red, which acts as a secretagogue here; however, baclofen‐induced inhibition was reduced significantly. Furthermore, baclofen produced no clear inhibition during high‐frequency mIPSCs bursts induced by the potent secretagogue α‐Latrotoxin. Together, these results suggest that GABAB inhibition occurs downstream of Ca2+ influx and may be mediated, in part, by an inhibition of the vesicular release mechanism.
Url:
DOI: 10.1111/j.1460-9568.2004.03505.x
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 001049
- to stream Istex, to step Curation: 000B84
- to stream Istex, to step Checkpoint: 000381
- to stream Main, to step Merge: 000994
- to stream Main, to step Curation: 000983
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mechanism of GABAB receptor‐mediated inhibition of spontaneous GABA release onto cerebellar Purkinje cells</title><author><name sortKey="Harvey, Victoria L" sort="Harvey, Victoria L" uniqKey="Harvey V" first="Victoria L." last="Harvey">Victoria L. Harvey</name></author><author><name sortKey="Stephens, Gary J" sort="Stephens, Gary J" uniqKey="Stephens G" first="Gary J." last="Stephens">Gary J. Stephens</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:7DC350BF401CA6A813C8B68DBF26085CAB2C2534</idno><date when="2004" year="2004">2004</date><idno type="doi">10.1111/j.1460-9568.2004.03505.x</idno><idno type="url">https://api.istex.fr/document/7DC350BF401CA6A813C8B68DBF26085CAB2C2534/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001049</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001049</idno><idno type="wicri:Area/Istex/Curation">000B84</idno><idno type="wicri:Area/Istex/Checkpoint">000381</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000381</idno><idno type="wicri:doubleKey">0953-816X:2004:Harvey V:mechanism:of:gabab</idno><idno type="wicri:Area/Main/Merge">000994</idno><idno type="wicri:Area/Main/Curation">000983</idno><idno type="wicri:Area/Main/Exploration">000983</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Mechanism of GABAB receptor‐mediated inhibition of spontaneous GABA release onto cerebellar Purkinje cells</title><author><name sortKey="Harvey, Victoria L" sort="Harvey, Victoria L" uniqKey="Harvey V" first="Victoria L." last="Harvey">Victoria L. Harvey</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Pharmacology, University College London, Gower Street, London WC1E 6BT</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Stephens, Gary J" sort="Stephens, Gary J" uniqKey="Stephens G" first="Gary J." last="Stephens">Gary J. Stephens</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Pharmacology, University College London, Gower Street, London WC1E 6BT</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Neuroscience</title><idno type="ISSN">0953-816X</idno><idno type="eISSN">1460-9568</idno><imprint><publisher>Blackwell Science Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2004-08">2004-08</date><biblScope unit="volume">20</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="684">684</biblScope><biblScope unit="page" to="700">700</biblScope></imprint><idno type="ISSN">0953-816X</idno></series><idno type="istex">7DC350BF401CA6A813C8B68DBF26085CAB2C2534</idno><idno type="DOI">10.1111/j.1460-9568.2004.03505.x</idno><idno type="ArticleID">EJN3505</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0953-816X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>GABAA receptor</term><term>baclofen</term><term>miniature inhibitory postsynaptic current</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">γ‐Aminobutyric acid (GABA)B receptor‐mediated modulation of spontaneous GABA release onto Purkinje cells was investigated in cerebellar slices from 3‐ to 5‐week‐old mice. The GABAB receptor agonists baclofen and CGP 44533 each reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs), with no significant effect on mIPSC amplitude; together, consistent with a presynaptic site of action. The GABAB receptor antagonist CGP 55845 blocked baclofen‐induced inhibition. The sulphydryl alkylating agent N‐ethylmaleimide occluded baclofen effects, implicating Gi/o subunits in mediating a GABAB G protein‐coupled receptor pathway. Baclofen‐induced inhibition persisted in the presence of Ba2+, a blocker of K+ channels, and Cd2+, a blocker of Ca2+ channel‐mediated GABA release. Application of nominally Ca2+‐free extracellular solutions reduced mIPSC frequency and amplitude; however, baclofen produced a significant inhibition in mIPSC frequency, further suggesting that this pathway was independent of Ca2+ influx. Spontaneous GABA release was increased by the adenylate cyclase activator, forskolin, and the phorbol ester, phorbol 12,13‐dibutyrate. However, baclofen‐induced inhibition was not significantly changed in either condition. Baclofen action was also not affected by the adenylate cyclase inhibitor SQ 22536 or the protein kinase C inhibitor chelerythrine chloride. Baclofen still reduced mIPSC frequency in the presence of the polyvalent cation ruthenium red, which acts as a secretagogue here; however, baclofen‐induced inhibition was reduced significantly. Furthermore, baclofen produced no clear inhibition during high‐frequency mIPSCs bursts induced by the potent secretagogue α‐Latrotoxin. Together, these results suggest that GABAB inhibition occurs downstream of Ca2+ influx and may be mediated, in part, by an inhibition of the vesicular release mechanism.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement><orgName><li>University College de Londres</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Harvey, Victoria L" sort="Harvey, Victoria L" uniqKey="Harvey V" first="Victoria L." last="Harvey">Victoria L. Harvey</name></region><name sortKey="Stephens, Gary J" sort="Stephens, Gary J" uniqKey="Stephens G" first="Gary J." last="Stephens">Gary J. Stephens</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Terre/explor/CobaltMaghrebV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000983 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000983 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Terre
|area= CobaltMaghrebV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:7DC350BF401CA6A813C8B68DBF26085CAB2C2534
|texte= Mechanism of GABAB receptor‐mediated inhibition of spontaneous GABA release onto cerebellar Purkinje cells
}}
| This area was generated with Dilib version V0.6.32. |  |