Processing of retinal signals in normal and HCN deficient mice.
Processing of retinal signals in normal and HCN deficient mice.
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DOI：
10.1371/journal.pone.0029812
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gargini C
中科院分区：
文献类型：
--
作者：
Della Santina L;Piano I;Cangiano L;Caputo A;Ludwig A;Cervetto L;Gargini C
本研究探讨了两种不同的HCN通道亚型在外视网膜光反应中的作用。利用HCN缺乏的小鼠模型和体外(膜片钳)和在体(ERG)视网膜活动记录，我们发现HCN1和HCN2通道在不同的视网膜部位表达，并发挥不同的功能。具体地说，HCN1主要在光感受器内节段水平工作，在那里，它们与其他电压敏感通道一起，控制对强光的反应的时间进程。相反，HCN2通道主要表达在双极细胞的树突上，并影响对暗光的反应。在hcn1−/−小鼠身上或在药物阻断ih期间的单细胞记录显示，与之前的报道相反，Ikx单独能够在杆状明亮闪光反应中产生快速初始瞬变。在这里，我们证明了Ih和Ikx对棒的时间调谐的相对贡献取决于膜电位。这是第一次在视网膜切片制备的单个细胞和完整动物的完整全场ERG反应中分析正常和HCN1或HCN2缺陷小鼠的光反应。这种比较揭示了单细胞电流钳数据和ERG测量之间的高度相关性。一张新的图片显示，视觉对暗淡和明亮亮度变化的反应的时间分布分别由光感受器和双极细胞中不同的电压依赖电导的协调选通决定。
This study investigates the role of two different HCN channel isoforms in the light response of the outer retina. Taking advantage of HCN-deficient mice models and of in vitro (patch-clamp) and in vivo (ERG) recordings of retinal activity we show that HCN1 and HCN2 channels are expressed at distinct retinal sites and serve different functions. Specifically, HCN1 operate mainly at the level of the photoreceptor inner segment from where, together with other voltage sensitive channels, they control the time course of the response to bright light. Conversely, HCN2 channels are mainly expressed on the dendrites of bipolar cells and affect the response to dim lights. Single cell recordings in HCN1−/− mice or during a pharmacological blockade of Ih show that, contrary to previous reports, Ikx alone is able to generate the fast initial transient in the rod bright flash response. Here we demonstrate that the relative contribution of Ih and Ikx to the rods' temporal tuning depends on the membrane potential. This is the first instance in which the light response of normal and HCN1- or HCN2-deficient mice is analyzed in single cells in retinal slice preparations and in integrated full field ERG responses from intact animals. This comparison reveals a high degree of correlation between single cell current clamp data and ERG measurements. A novel picture emerges showing that the temporal profile of the visual response to dim and bright luminance changes is separately determined by the coordinated gating of distinct voltage dependent conductances in photoreceptors and bipolar cells.
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