Speier S, Yang S-B, Sroka K, Rose T, Rupnik M
European Neuroscience Institute Göttingen, Waldweg 33, 37073 Göttingen, Germany.
Mol Cell Endocrinol. 2005 Jan 31;230(1-2):51-8. doi: 10.1016/j.mce.2004.11.002.
In pancreatic beta-cells, inhibition of K(ATP)-channels plays a pivotal role in signal transduction of glucose-induced insulin release. However, the extreme sensitivity of K(ATP)-channels to its ligand ATP as found in inside-out patches is not directly compatible with modulation of these channels at physiological ATP. We studied K(ATP)-channel sensitivity to ATP in beta-cells in dispersed culture and in fresh pancreatic tissue slices. Physiological ATP blocks more than 99% of K(ATP)-channels in cultured beta-cells, while only 90% in beta-cells in slices, indicating reduced sensitivity to ATP in the fresh slices. Applying cytosolic factors like ADP, phosphatidylinositol-4,5-bisphosphate (PIP(2)) or oleoyl-CoA did not restore the K(ATP)-channel sensitivity in cultured beta-cells. Our data suggest that interaction between SUR1 and Kir6.2 subunit of the K(ATP)-channel could be a factor in sensitivity modulation. Tissue slices are the first beta-cell preparation to study direct K(ATP)-channel modulation by physiological ATP.
在胰腺β细胞中，抑制ATP敏感性钾通道（K(ATP)通道）在葡萄糖诱导的胰岛素释放信号转导中起关键作用。然而，如在膜外翻片膜中所发现的，K(ATP)通道对其配体ATP的极端敏感性与这些通道在生理细胞内ATP浓度（ATP）下的调节并不直接相符。我们研究了分散培养的β细胞和新鲜胰腺组织切片中K(ATP)通道对ATP的敏感性。生理ATP可阻断培养的β细胞中超过99%的K(ATP)通道，而在切片中的β细胞中仅阻断90%，这表明新鲜切片中对ATP的敏感性降低。应用胞质因子如ADP、磷脂酰肌醇-4,5-二磷酸（PIP(2)）或油酰辅酶A并不能恢复培养的β细胞中K(ATP)通道的敏感性。我们的数据表明，K(ATP)通道的磺脲类受体1（SUR1）和内向整流钾通道6.2（Kir6.2）亚基之间的相互作用可能是敏感性调节的一个因素。组织切片是首个用于研究生理ATP对K(ATP)通道直接调节作用的β细胞制剂。
