HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 577/2/497    most recent jphysiol.2006.118141v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Deng, P.-Y. Articles by Lei, S. Search for Related Content PubMed PubMed Citation Articles by Deng, P.-Y. Articles by Lei, S. Related Collections Cellular

¹ Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA
² Division of Life Sciences, Korea Institute of Science and Technology, Seoul 136-791, Korea

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_q/11, but were independent of its known downstream effectors, a direct coupling may exist between G_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.

(Received 27 July 2006; accepted after revision 19 September 2006; first published online 21 September 2006)
Corresponding author S. Lei: Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58203, USA. Email: slei{at}medicine.nodak.edu

This article has been cited by other articles:

				S. Lei, P.-Y. Deng, J. E. Porter, and H.-S. Shin Adrenergic Facilitation of GABAergic Transmission in Rat Entorhinal Cortex J Neurophysiol, November 1, 2007; 98(5): 2868 - 2877. [Abstract] [Full Text] [PDF]

				P.-Y. Deng, S. K. S. Poudel, L. Rojanathammanee, J. E. Porter, and S. Lei Serotonin Inhibits Neuronal Excitability by Activating Two-Pore Domain K+ Channels in the Entorhinal Cortex Mol. Pharmacol., July 1, 2007; 72(1): 208 - 218. [Abstract] [Full Text] [PDF]

				P.-Y. Deng and S. Lei Long-Term Depression in Identified Stellate Neurons of Juvenile Rat Entorhinal Cortex J Neurophysiol, January 1, 2007; 97(1): 727 - 737. [Abstract] [Full Text] [PDF]