Functional presynaptic HCN channels in the rat globus pallidus
Functional presynaptic HCN channels in the rat globus pallidus
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DOI：
10.1111/j.1460-9568.2007.05463.x
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发表时间：
2007-04-01
影响因子：
3.4
通讯作者：
Stanford, Ian M.
中科院分区：
文献类型：
--
作者：
Boyes, Justin;Bolam, J. Paul;Stanford, Ian M.
超极化激活的环核苷酸门控阳离子通道(HCN)在啮齿动物苍白球(GP)突触后表达，在控制GP神经元活动中起着重要作用。为了进一步阐明HCN通道在GP中的作用，本研究用免疫细胞化学和电生理方法验证了在GP神经元的局部轴突侧支上也有HCN通道在突触前表达的假设。在电子显微镜水平上，HCN1和HCN2的免疫过氧化物酶标记定位于GP胞体和树突、有髓和无髓轴突以及轴突终末。一组标记的终末与胞体和近端树突形成对称性突触，小白蛋白免疫反应阳性，与GABA能GP投射神经元的轴突侧支一致。此外，在形成非对称突触的轴突终末也观察到了HCN1的标记，但对囊泡谷氨酸转运蛋白2的免疫反应较弱。免疫金标记法显示，HCN1和HCN1主要位于两种类型终末的突触外部位。为了确定突触前HCN通道在GP中的功能，我们在体外进行了GP神经元的全细胞记录。应用HCN通道阻断剂ZD7288可使mIPSCs频率增加，但对其幅度无影响，提示HCN通道对GABA的释放具有调性调节作用。它们的存在和预测在调节递质释放中的作用，代表了一种迄今未知的机制，即HCN通道影响GP神经元的活动。
Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are expressed postsynaptically in the rodent globus pallidus (GP), where they play several important roles in controlling GP neuronal activity. To further elucidate the role of HCN channels in the GP, immunocytochemical and electrophysiological approaches were used to test the hypothesis that HCN channels are also expressed presynaptically on the local axon collaterals of GP neurons. At the electron microscopic level, immunoperoxidase labelling for HCN1 and HCN2 was localized in GP somata and dendritic processes, myelinated and unmyelinated axons, and axon terminals. One population of labelled terminals formed symmetric synapses with somata and proximal dendrites and were immunoreactive for parvalbumin, consistent with the axon collaterals of GABAergic GP projection neurons. In addition, labelling for HCN2 and, to a lesser degree, HCN1 was observed in axon terminals that formed asymmetric synapses and were immunoreactive for the vesicular glutamate transporter 2. Immunogold labelling demonstrated that HCN1 and HCN2 were located predominantly at extrasynaptic sites along the plasma membrane of both types of terminal. To determine the function of presynaptic HCN channels in the GP, we performed whole-cell recordings from GP neurons in vitro. Bath application of the HCN channel blocker ZD7288 resulted in an increase in the frequency of mIPSCs but had no effect on their amplitude, implying that HCN channels tonically regulate the release of GABA. Their presence, and predicted role in modulating transmitter release, represents a hitherto unidentified mechanism whereby HCN channels influence the activity of GP neurons.