RGD Reference Report - Thyrotropin-releasing hormone increases GABA release in rat hippocampus. - Rat Genome Database

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Thyrotropin-releasing hormone increases GABA release in rat hippocampus.

Authors: Deng, PY  Porter, JE  Shin, HS  Lei, S 
Citation: Deng PY, etal., J Physiol. 2006 Dec 1;577(Pt 2):497-511. Epub 2006 Sep 21.
RGD ID: 1600408
Pubmed: PMID:16990402   (View Abstract at PubMed)
PMCID: PMC1890442   (View Article at PubMed Central)
DOI: DOI:10.1113/jphysiol.2006.118141   (Journal Full-text)

Thyrotropin-releasing hormone (TRH) is a tripeptide that is widely distributed in the brain including the hippocampus where TRH receptors are also expressed. TRH has anti-epileptic effects and regulates arousal, sleep, cognition, locomotion and mood. However, the cellular mechanisms underlying such effects remain to be determined. We examined the effects of TRH on GABAergic transmission in the hippocampus and found that TRH increased the frequency of GABAA receptor-mediated spontaneous IPSCs in each region of the hippocampus but had no effects on miniature IPSCs or evoked IPSCs. TRH increased the action potential firing frequency recorded from GABAergic interneurons in CA1 stratum radiatum and induced membrane depolarization suggesting that TRH increases the excitability of interneurons to facilitate GABA release. TRH-induced inward current had a reversal potential close to the K+ reversal potential suggesting that TRH inhibits resting K+ channels. The involved K+ channels were sensitive to Ba2+ but resistant to other classical K+ channel blockers, suggesting that TRH inhibits the two-pore domain K+ channels. Because the effects of TRH were mediated via Galphaq/11, but were independent of its known downstream effectors, a direct coupling may exist between Galphaq/11 and K+ channels. Inhibition of the function of dynamin slowed the desensitization of TRH responses. TRH inhibited seizure activity induced by Mg2+ deprivation, but not that generated by picrotoxin, suggesting that TRH-mediated increase in GABA release contributes to its anti-epileptic effects. Our results demonstrate a novel mechanism to explain some of the hippocampal actions of TRH.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of gamma-aminobutyric acid secretion  IDA 1600408 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Trh  (thyrotropin releasing hormone)


Additional Information