Thyrotropin-releasing hormone increases GABA release in rat hippocampus


By jpeza - Posted on 24 Marzo 2009

Fecha Publicación: 
3 Ene 2006
Nombre de Revista: 
Datos del paper
Volumen: 
577
Issue: 
2
Página Inicial: 
497
Página Final: 
511
Abstract: 

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 CAl stratum radiatllm and induced membrane depolarization suggesting that TRH increases the excitability of interneurons to facilitate GABA release. TRH-indllced inward current had a reversal potential close to the K+ reversal potential suggesting that TRH inhibits resting K+ chan nels. The involved K+ channels were sensitive to BaH but resistant to other classical K+ channel blockers, suggesting that TRH inhibits the two-pore domain K+ channels. Because the effects ofTRH were mediated via Gaq/II, but were independent of its known downstream effectors, a direct coupling may exist between Gaq/ll and K+ channels. Inhibition of the function of dynamin slowed the desensitization of TRH responses. TRH inhibited seizure activity induced by MgH deprivation, but not that generated by picrotoxin, suggesting that TRH-mediated increase in GAB A release contributes to its anti-epileptic effects. Our results demonstrate a novel mechanism to explain some of the hppocamoal actions ofTRH.

Dirección del Autor: 

Department of Pharmacology. Physiology and Therapeutics. Sthool ofMedit"ine and Health Sciences. University of North Dakota. Grand Forks. ND 58203. USA

Division of Life Sciences. Korea Institute of Science and Technology, Seoul 136-791. Korea

Coautores: 

Pan- Yue Deng, James E. Porter, Hee-Sup Shin and Saobo Lei

Clasificación del paper: 
tripeptide (TRH) ; Hormone
AdjuntoTamaño
[file] Journal_of_Physiology_2006_vol 577_num 1_ pp 497-511.pdf1.87 MB