title: Neurotensinergic Excitation of Dentate Gyrus Granule Cells via Gαq-Coupled Inhibition of TASK-3 Channels.
abstract: Neurotensin (NT) is a 13-amino acid peptide and serves as a neuromodulator in the brain. Whereas NT has been implicated in learning and memory, the underlying cellular and molecular mechanisms are ill-defined. Because the dentate gyrus receives profound innervation of fibers containing NT and expresses high density of NT receptors, we examined the effects of NT on the excitability of dentate gyrus granule cells (GCs). Our results showed that NT concentration dependently increased action potential (AP) firing frequency of the GCs by the activation of NTS1 receptors resulting in the depolarization of the GCs. NT-induced enhancement of AP firing frequency was not caused indirectly by releasing glutamate, GABA, acetylcholine, or dopamine, but due to the inhibition of TASK-3 K(+) channels. NT-mediated excitation of the GCs was G protein dependent, but independent of phospholipase C, intracellular Ca(2+) release, and protein kinase C. Immunoprecipitation experiment demonstrates that the activation of NTS1 receptors induced the association of Gαq/11 and TASK-3 channels suggesting a direct coupling of Gαq/11 to TASK-3 channels. Endogenously released NT facilitated the excitability of the GCs contributing to the induction of long-term potentiation at the perforant path-GC synapses. Our results provide a cellular mechanism that helps to explain the roles of NT in learning and memory.
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Haopeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Cilz
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: Lalitha
authors.initials: L
authors.lastname: Kurada
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: Binqi
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, Tokyo, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Wada
authors.affiliation: Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bayliss
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Porter
authors.affiliation: Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: Saobo
authors.initials: S
authors.lastname: Lei
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009496:Neurotensin / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000235:genetics / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: C407082:Kcnk9 protein, rat; C490984:Ntsr2 protein, mouse; C099727:Ntsr2 protein, rat; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D018028:Receptors, Neurotensin; C511784:TASK3 protein, mouse; C114036:neurotensin type 1 receptor; D009496:Neurotensin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
keywords: channel; depolarization; glutamate; hippocampus; memory; peptide; synapse; synaptic transmission