Deng, Pan-Yue Porter, James E. Shin, Hee-Sup Lei, Saobo 2024-01-21T02:00:32Z 2024-01-21T02:00:32Z 2021-09-01 2006-12-01 0022-3751 https://pubs.kist.re.kr/handle/201004/134832 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 GABA(A) 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 G alpha(q/11), but were independent of its known downstream effectors, a direct coupling may exist between G alpha(q/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. English WILEY CENTRAL-NERVOUS-SYSTEM K+ CHANNEL POTASSIUM CHANNEL PHOSPHOLIPASE-C PITUITARY-CELLS TASK-1 KCNK3 RECEPTORS TRH MOTONEURONS MODULATION Thyrotropin-releasing hormone increases GABA release in rat hippocampus Article 10.1113/jphysiol.2006.118141 1 JOURNAL OF PHYSIOLOGY-LONDON, v.577, no.2, pp.497 - 511 JOURNAL OF PHYSIOLOGY-LONDON 577 2 497 511 scie scopus 000242240900004 2-s2.0-33751347627 Neurosciences Physiology Neurosciences & Neurology Physiology Article CENTRAL-NERVOUS-SYSTEM K+ CHANNEL POTASSIUM CHANNEL PHOSPHOLIPASE-C PITUITARY-CELLS TASK-1 KCNK3 RECEPTORS TRH MOTONEURONS MODULATION