Nemec J, Wickman K, Clapham D E
Department of Cardiology and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Biophys J. 1999 Jan;76(1 Pt 1):246-52. doi: 10.1016/S0006-3495(99)77193-6.
IKACh is an inwardly rectifying potassium channel that plays an important role in the regulation of mammalian heart rate. IKACh is activated by direct interaction with Gbetagamma subunits of pertussis toxin-sensitive heterotrimeric G-proteins. The stoichiometry of the Gbetagamma/channel complex is currently unknown, and kinetic analysis of the channel behavior has led to conflicting conclusions. Here, we analyze the kinetics of the native IKACh channel in inside-out cardiomyocyte patches activated directly by Gbetagamma. We conclude that the channel has at least two open states and that binding of Gbetagamma prolongs its mean open time duration. These findings imply the existence of at least two binding sites on the channel complex for Gbetagamma. We also show that the duration of the channel opening is negatively correlated with the duration of subsequent channel closing, which further constrains the possible kinetic models. A simple qualitative model describing the kinetic behavior of IKACh is presented.
内向整流钾通道（IKACh）是一种内向整流钾通道，在调节哺乳动物心率方面发挥着重要作用。IKACh通过与百日咳毒素敏感的异源三聚体G蛋白的Gβγ亚基直接相互作用而被激活。目前尚不清楚Gβγ/通道复合物的化学计量，并且对通道行为的动力学分析得出了相互矛盾的结论。在这里，我们分析了在由Gβγ直接激活的内面向外心肌细胞贴片中原发性IKACh通道的动力学。我们得出结论，该通道至少有两个开放状态，并且Gβγ的结合延长了其平均开放时间。这些发现意味着通道复合物上至少存在两个Gβγ结合位点。我们还表明，通道开放的持续时间与随后通道关闭的持续时间呈负相关，这进一步限制了可能的动力学模型。本文提出了一个描述IKACh动力学行为的简单定性模型。
