GIRK channel activation involves a local rearrangement of a preformed G protein channel complex
GIRK channel activation involves a local rearrangement of a preformed G protein channel complex
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DOI：
10.1016/j.neuron.2006.08.017
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发表时间：
2006-09-07
期刊：
影响因子：
16.2
通讯作者：
Reuveny, Eitan
中科院分区：
文献类型：
--
作者：
Riven, Inbal;Iwanir, Shachar;Reuveny, Eitan
G蛋白偶联信号是控制细胞兴奋性的主要机制之一。在突触后膜的这种控制的主要目标之一是G蛋白偶联钾通道（GIRK/Kir 3），其在百日咳毒素敏感性G蛋白偶联受体激活后产生缓慢的抑制性突触后电位。使用全内反射荧光（TIRF）显微镜结合荧光共振能量转移（FRET），在完整的细胞中，我们提供的证据存在的三聚体G蛋白通道复合物在休息。我们表明，通过受体激活的通道诱导G蛋白的局部构象开关，以诱导通道开放。因此，这种复合物的存在提供了精确的时间和高度选择性激活通道的手段，这是神经元兴奋性微调所需的。
G protein-coupled signaling is one of the major mechanisms for controlling cellular excitability. One of the main targets for this control at postsynaptic membranes is the G protein-coupled potassium channels (GIRK/Kir3), which generate slow inhibitory postsynaptic potentials following the activation of Pertussis toxin-sensitive G protein-coupled receptors. Using total internal reflection fluorescence (TIRF) microscopy combined with fluorescence resonance energy transfer (FRET), in intact cells, we provide evidence for the existence of a trimeric G protein-channel complex at rest. We show that activation of the channel via the receptor induces a local conformational switch of the G protein to induce channel opening. The presence of such a complex thus provides the means for a precise temporal and highly selective activation of the channel, which is required for fine tuning of neuronal excitability.