多巴胺耗竭诱导的HCN3上调增强了基底神经节输出神经元的反弹兴奋性。

Dopamine depletion induced up-regulation of HCN3 enhances rebound excitability of basal ganglia output neurons.

作者信息

Meurers Bernhard H, Dziewczapolski Gustavo, Bittner Anton, Shi Tao, Kamme Fredrik, Shults Clifford W

机构信息

Department of Neurology, University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095, USA.

出版信息

Neurobiol Dis. 2009 Apr;34(1):178-88. doi: 10.1016/j.nbd.2009.01.007.

DOI:10.1016/j.nbd.2009.01.007

PMID:19320057

Abstract

Motor symptoms in Parkinson's disease (PD) are associated with complex changes of firing properties in basal ganglia output neurons (BGON). The abnormalities are generally attributed to altered synaptic input and potential post-synaptic mechanisms are currently unknown. Our cell-type selective transcriptome analyses of BGON in the rat 6-hydroxydopamine (6-OHDA) model of PD identified the ion channel HCN3 as a likely contributor to altered neuronal excitability. Quantitative PCR experiments confirmed the HCN3 upregulation in the rat and mouse 6-OHDA models and also demonstrated selectivity of the effect for HCN3. In accordance with the mRNA expression data, in vitro whole cell patch-clamp recordings in BGON showed increased HCN3 current amplitudes and increased rebound excitability in BGON of 6-OHDA treated rats. These data establish HCN3 up-regulation as a novel candidate mechanism that might contribute to the in vivo changes of electrical activity in basal ganglia output neurons of the parkinsonian brain.

摘要

帕金森病（PD）中的运动症状与基底神经节输出神经元（BGON）放电特性的复杂变化有关。这些异常通常归因于突触输入的改变，而潜在的突触后机制目前尚不清楚。我们对大鼠6-羟基多巴胺（6-OHDA）帕金森病模型中的BGON进行的细胞类型选择性转录组分析确定离子通道HCN3可能是神经元兴奋性改变的一个因素。定量PCR实验证实了大鼠和小鼠6-OHDA模型中HCN3的上调，并且还证明了该效应对HCN3的选择性。根据mRNA表达数据，BGON的体外全细胞膜片钳记录显示，6-OHDA处理的大鼠的BGON中HCN3电流幅度增加，反弹兴奋性增强。这些数据表明HCN3上调是一种新的候选机制，可能导致帕金森病大脑基底神经节输出神经元体内电活动的变化。