Neurotensinergic augmentation of glutamate release at the perforant path-granule cell synapse in rat dentate gyrus: Roles of L-Type Ca2+ channels, calmodulin and myosin light-chain kinase

NEUROPHARMACOLOGY

卷:95

Article

Zhang, Haopeng^1,2  Dong, Hailong²  Lei, Saobo¹ 

[1] Univ N Dakota, Sch Med & Hlth Sci, Dept Basic Sci, Grand Forks, ND 58203 USA

[2] Fourth Mil Med Univ, Xijing Hosp, Dept Anesthesiol, Xian, Shaanxi Provinc, Peoples R China

关键词: Synapse;    Ca2+ channels;    Ca2+;    Hippocampus;    G proteins;    Synaptic transmission;    glutamate;    Alzheimer's disease;    Myosin light chain kinase;   

DOI  :  10.1016/j.neuropharm.2015.03.028

来源: Elsevier

【 摘 要 】

Neurotensin (NT) serves as a neuromodulator in the brain where it is involved in modulating a variety of physiological functions including nociception, temperature, blood pressure and cognition, and many neurological diseases such as Alzheimer's disease, schizophrenia and Parkinson's disease. Whereas there is compelling evidence demonstrating that NT facilitates cognitive processes, the underlying cellular and molecular mechanisms have not been fully determined. Because the dentate gyrus expresses high densities of NT and NT receptors, we examined the effects of NT on the synaptic transmission at the synapse formed between the perforant path (PP) and granule cells (GC) in the rats. Our results demonstrate that NT persistently increased the amplitude of the AMPA receptor-mediated EPSCs at the PP-GC synapse. NT-induced increases in AMPA EPSCs were mediated by presynaptic NTS1 receptors. NT reduced the coefficient of variation and paired-pulse ratio of AMPA EPSCs suggesting that NT facilitates presynaptic glutamate release. NT increased the release probability and the number of readily releasable vesicles with no effects on the rate of recovery from vesicle depletion. NT-mediated augmentation of glutamate release required the influx of Ca2+ via L-type Ca2+ channels and the functions of calmodulin and myosin light chain kinase. Our results provide a cellular and molecular mechanism to explain the roles of NT in the hippocampus. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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