Leist Michael, Datunashvilli Maia, Kanyshkova Tatyana, Zobeiri Mehrnoush, Aissaoui Ania, Cerina Manuela, Romanelli Maria Novella, Pape Hans-Christian, Budde Thomas
Institut für Physiologie I, Westfälische Wilhelms-Universität, Robert-Koch-Str. 27a, 48149 Münster, Germany.
Laboratory of Sleep-Wakefulness Cycle Studies, Faculty of Arts and Science, Ilia State University, Kakutsa Cholokashvili Ave 3/5, Tbilisi 0162, Georgia.
Sci Rep. 2016 Apr 28;6:24904. doi: 10.1038/srep24904.
Although hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels and the corresponding h-current (Ih) have been shown to fundamentally shape the activity pattern in the thalamocortical network, little is known about their function in local circuit GABAergic interneurons (IN) of the dorsal part of the lateral geniculate nucleus (dLGN). By combining electrophysiological, molecular biological, immunohistochemical and cluster analysis, we characterized the properties of Ih and the expression profile of HCN channels in IN. Passive and active electrophysiological properties of IN differed. Two subclasses of IN were resolved by unsupervised cluster analysis. Small cells were characterized by depolarized resting membrane potentials (RMP), stronger anomalous rectification, higher firing frequency of faster action potentials (APs), appearance of rebound bursting, and higher Ih current density compared to the large IN. The depolarization exerted by sustained HCN channel activity facilitated neuronal firing. In addition to cyclic nucleotides, Ih in IN was modulated by PIP2 probably based on the abundant expression of the HCN3 isoform. Furthermore, only IN with larger cell diameters expressed neuronal nitric oxide synthase (nNOS). It is discussed that Ih in IN is modulated by neurotransmitters present in the thalamus and that the specific properties of Ih in these cells closely reflect their modulatory options.
尽管超极化激活的环核苷酸门控阳离子(HCN)通道及相应的h电流(Ih)已被证明在丘脑皮质网络活动模式的形成中起根本作用,但对于它们在外侧膝状体背侧部(dLGN)局部回路GABA能中间神经元(IN)中的功能却知之甚少。通过结合电生理、分子生物学、免疫组织化学和聚类分析,我们对IN中Ih的特性及HCN通道的表达谱进行了表征。IN的被动和主动电生理特性有所不同。通过无监督聚类分析解析出了两类IN。与大的IN相比,小细胞的特征在于静息膜电位(RMP)去极化、更强的反常整流、更快动作电位(AP)的更高发放频率、出现反弹爆发以及更高的Ih电流密度。持续的HCN通道活动所产生的去极化促进了神经元的发放。除了环核苷酸外,IN中的Ih可能基于HCN3亚型的丰富表达而受到磷脂酰肌醇-4,5-二磷酸(PIP2)的调节。此外,只有细胞直径较大的IN表达神经元型一氧化氮合酶(nNOS)。本文讨论了IN中的Ih受丘脑中存在的神经递质调节,且这些细胞中Ih的特定特性密切反映了它们的调节方式。