Thomzig A, Wenzel M, Karschin C, Eaton M J, Skatchkov S N, Karschin A, Veh R W
Institut für Anatomie der Charité, Medizinische Fakultät der Humboldt-Universität zu Berlin, Philippstrasse 12, D-10098 Berlin, Germany.
Mol Cell Neurosci. 2001 Dec;18(6):671-90. doi: 10.1006/mcne.2001.1048.
ATP-sensitive potassium channels (K-ATP channels) directly couple the energy state of a cell to its excitability, are activated by hypoxia, and have been suggested to protect neurons during disturbances of energy metabolism such as transient ischemic attacks or stroke. Molecular studies have demonstrated that functional K-ATP channels are octameric protein complexes, consisting of four sulfonylurea receptor proteins and four pore-forming subunits which are members of the Kir6 family of inwardly rectifying potassium channels. Here we show, using specific antibodies against the two known pore-forming subunits (Kir6.1 and Kir6.2) of K-ATP channels, that only Kir6.1 and not Kir6.2 subunits are expressed in astrocytes. In addition to a minority of neurons, Kir6.1 protein is present on hippocampal, cortical, and cerebellar astrocytes, tanycytes, and Bergmann glial cells. We also provide ultrastructural evidence that Kir6.1 immunoreactivity is primarily localized to distal perisynaptic and peridendritic astrocyte plasma membrane processes, and we confirm the presence of functional K-ATP channels in Bergmann glial cells by slice-patch-clamp experiments. The identification of Kir6.1 as the principal pore-forming subunit of plasma membrane K-ATP channels in astrocytes suggests that these glial K-ATP channels act in synergy with neuronal Kir6.2-mediated K-ATP channels during metabolic challenges in the brain.
ATP敏感性钾通道（K-ATP通道）直接将细胞的能量状态与其兴奋性相耦合，可被缺氧激活，并且有人提出其在诸如短暂性脑缺血发作或中风等能量代谢紊乱期间对神经元具有保护作用。分子研究表明，功能性K-ATP通道是八聚体蛋白复合物，由四个磺脲类受体蛋白和四个孔形成亚基组成，这些亚基是内向整流钾通道Kir6家族的成员。在此，我们使用针对K-ATP通道两个已知孔形成亚基（Kir6.1和Kir6.2）的特异性抗体表明，仅Kir6.1而非Kir6.2亚基在星形胶质细胞中表达。除少数神经元外，Kir6.1蛋白存在于海马、皮质和小脑的星形胶质细胞、伸长细胞和伯格曼胶质细胞上。我们还提供了超微结构证据，表明Kir6.1免疫反应性主要定位于突触周围和树突周围星形胶质细胞质膜的远端突起，并且我们通过脑片膜片钳实验证实了伯格曼胶质细胞中存在功能性K-ATP通道。星形胶质细胞质膜K-ATP通道主要孔形成亚基为Kir6.1这一发现表明，在大脑代谢挑战期间，这些胶质K-ATP通道与神经元Kir6.2介导的K-ATP通道协同发挥作用。
