Larsson O, Barker C J, Berggren P O
Department of Molecular Medicine, Rolf Luft Center for Diabetes Research, Karolinska Institute, Stockholm, Sweden.
Diabetes. 2000 Sep;49(9):1409-12. doi: 10.2337/diabetes.49.9.1409.
Phosphatidylinositol 4,5-bisphosphate (PIP2) has been suggested to play an important role as an endogenous regulator of ATP-sensitive potassium (KATP) channels consisting of Kir6.2 as a pore-forming subunit. These studies show the ability of PIP2 to activate KATP channel activity and to counteract the inhibitory effect of ATP, implying that PIP2 could serve the function of modulating the sensitivity of KATP channels to the cytoplasmic free ATP concentration. Careful examination of the literature reveals that the definitive physiologically relevant experiments to establish efficacy of PIP2 on this channel may still have to be performed. Our reservations are based on the handling of PIP2 in cell-free experiments and in various strategies designed to modulate PIP2 concentrations in intact cells. Furthermore, a potent stimulatory effect of phosphatidylinositol 3,4,5trisphosphate, a downstream metabolite of PIP2, on KATP channel activity raises the possibility that the effects on the KATP channel may not be directly related to PIP2.
磷脂酰肌醇4,5 - 二磷酸（PIP2）被认为作为由Kir6.2作为孔形成亚基的ATP敏感性钾通道（KATP）的内源性调节剂发挥重要作用。这些研究表明PIP2具有激活KATP通道活性以及抵消ATP抑制作用的能力，这意味着PIP2可能起到调节KATP通道对细胞质游离ATP浓度敏感性的作用。仔细查阅文献发现，确定PIP2对该通道有效性的具有生理学相关性的确切实验可能仍需进行。我们的保留意见基于无细胞实验中对PIP2的处理以及旨在调节完整细胞中PIP2浓度的各种策略。此外，PIP2的下游代谢产物磷脂酰肌醇3,4,5 - 三磷酸对KATP通道活性具有强大的刺激作用，这增加了对KATP通道的影响可能与PIP2没有直接关系的可能性。
