Pore‐forming subunits of K‐ATP channels, Kir6.1 and Kir6.2, display prominent differences in regional and cellular distribution in the rat brain
Pore‐forming subunits of K‐ATP channels, Kir6.1 and Kir6.2, display prominent differences in regional and cellular distribution in the rat brain
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DOI：
10.1002/cne.20469
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发表时间：
2005-04
影响因子：
2.5
通讯作者：
A. Thomzig;G. Laube;H. Prüss;R. Veh
中科院分区：
文献类型：
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作者：
A. Thomzig;G. Laube;H. Prüss;R. Veh
K-ATP 通道由两个结构不同的亚基组成：Kir6.0 家族的成孔亚基（Kir6.1 或 Kir6.2）和具有调节活性的磺酰脲受体（SUR1、SUR2、SUR2A、SUR2B）。大脑中 K-ATP 通道的功能多样性广泛，对于神经元活动至关重要。在这里，我们使用针对 Kir6.1 和 Kir6.2 亚基的单特异性抗体进行免疫细胞化学分析，分析了成年大鼠大脑中这两种蛋白质的区域和细胞分布。我们发现 Kir6.2 在所有大脑区域中广泛表达，表明 Kir6.2 亚基在大多数神经元中形成 K-ATP 通道的孔，可能在低血糖或缺血等细胞应激条件下保护细胞。特别是在下丘脑核中，特别是腹内侧核和弓状核中，神经元仅表现出 Kir6.2 免疫反应性，表明 Kir6.2 是下丘脑葡萄糖反应神经元中 K-ATP 通道的成孔亚基。相比之下，Kir6.1 样免疫标记仅限于大鼠大脑大部分区域的星形胶质细胞（Thomzig 等人 [2001] Mol Cell Neurosci 18:671–690），而在神经元中非常弱或不存在。仅在不同的细胞核或神经元亚群中检测到中度甚至强的 Kir6.1 染色。这些 K-ATP 通道的生物学功能仍需阐明。 J.Comp。内罗尔。 484:313–330, 2005。© 2005 Wiley-Liss, Inc.
K‐ATP channels consist of two structurally different subunits: a pore‐forming subunit of the Kir6.0‐family (Kir6.1 or Kir6.2) and a sulfonylurea receptor (SUR1, SUR2, SUR2A, SUR2B) with regulatory activity. The functional diversity of K‐ATP channels in brain is broad and of fundamental importance for neuronal activity. Here, using immunocytochemistry with monospecific antibodies against the Kir6.1 and Kir6.2 subunits, we analyze the regional and cellular distribution of both proteins in the adult rat brain. We find Kir6.2 to be widely expressed in all brain regions, suggesting that the Kir6.2 subunit forms the pore of the K‐ATP channels in most neurons, presumably protecting the cells during cellular stress conditions such as hypoglycemia or ischemia. Especially in hypothalamic nuclei, in particular the ventromedial and arcuate nucleus, neurons display Kir6.2 immunoreactivity only, suggesting that Kir6.2 is the pore‐forming subunit of the K‐ATP channels in the glucose‐responsive neurons of the hypothalamus. In contrast, Kir6.1‐like immunolabeling is restricted to astrocytes (Thomzig et al. [2001] Mol Cell Neurosci 18:671–690) in most areas of the rat brain and very weak or absent in neurons. Only in distinct nuclei or neuronal subpopulations is a moderate or even strong Kir6.1 staining detected. The biological functions of these K‐ATP channels still need to be elucidated. J. Comp. Neurol. 484:313–330, 2005. © 2005 Wiley‐Liss, Inc.