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海马醚-α--go-go1 钾通道阻断:在惊跳反射和前脉冲抑制中的作用。

Hippocampal ether-à-go-go1 potassium channels blockade: effects in the startle reflex and prepulse inhibition.

机构信息

Department of Morphology Physiology and Basic Pathology, University of São Paulo (USP), Dental School of Ribeirão Preto, Brazil.

Federal University of São Paulo (UNIFESP), Brazil.

出版信息

Neurosci Lett. 2014 Jan 24;559:13-7. doi: 10.1016/j.neulet.2013.11.026. Epub 2013 Nov 24.

DOI:10.1016/j.neulet.2013.11.026
PMID:24284010
Abstract

Recently, our group described the ether-à-go-go1(Eag1) voltage-gated potassium (K(+)) channel (Kv10.1) expression in the dopaminergic cells indicating that these channels are part of the diversified group of ion channels related to dopaminergic neurons function. The increase of dopamine neurotransmission induces a reduction in the prepulse inhibition (PPI) of the acoustic startle reflex in rodents, which is a reliable index of sensorimotor gating deficits. The PPI response has been reported to be abnormally reduced in schizophrenia patients. The role of Eag1 K(+) channels in the PPI reaction had not been revealed until now, albeit the singular distribution of Eag1 in the dentate gyrus of the hippocampus and the hippocampal regulation of the startle reflex and PPI. The aim of this work was to investigate if Eag1 blockade on hippocampus modifies the PPI-disruptive effects of apomorphine in Wistar rats. Bilateral injection of anti-Eag1 single-chain antibody into the dentate gyrus of hippocampus did not modify apomorphine-disruptive effects in the PPI response. However, Eag1 antibody completely restored the startle amplitude decrease revealed after dentate gyrus surgery. These potentially biological important phenomenon merits further investigation regarding the role of Eag1 K(+) channels, mainly, on startle reflex modulation, since the physiological role of these channels remain obscure.

摘要

最近,我们的研究小组描述了在多巴胺能细胞中存在的醚-α-go-go1(Eag1)电压门控钾(K(+))通道(Kv10.1)的表达,表明这些通道是与多巴胺能神经元功能相关的多样化离子通道群体的一部分。多巴胺神经递质的增加会导致啮齿动物听觉惊跳反射的前脉冲抑制(PPI)减少,这是一种可靠的感觉运动门控缺陷的指标。已经报道精神分裂症患者的 PPI 反应异常降低。尽管 Eag1 在海马齿状回中的独特分布以及海马对惊跳反射和 PPI 的调节,但直到现在,Eag1 K(+)通道在 PPI 反应中的作用仍未被揭示。本工作旨在研究 Eag1 阻断海马是否会改变阿扑吗啡对 Wistar 大鼠 PPI 的破坏作用。将抗 Eag1 单链抗体双侧注射到海马齿状回不会改变阿扑吗啡对 PPI 反应的破坏作用。然而,Eag1 抗体完全恢复了齿状回手术后出现的惊跳幅度降低。这些具有潜在生物学意义的现象值得进一步研究 Eag1 K(+)通道的作用,特别是在惊跳反射调节方面,因为这些通道的生理作用仍然不清楚。

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