Barber David M, Schönberger Matthias, Burgstaller Jessica, Levitz Joshua, Weaver C David, Isacoff Ehud Y, Baier Herwig, Trauner Dirk
Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstraße 5-13, 81377 Munich, Germany.
Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany.
Chem Sci. 2016;7(3):2347-2352. doi: 10.1039/C5SC04084A. Epub 2015 Nov 23.
G-protein coupled inwardly rectifying potassium channels (GIRKs) are ubiquitously expressed throughout the human body and are an integral part of inhibitory signal transduction pathways. Upon binding of G subunits released from G-protein coupled receptors (GPCRs), GIRK channels open and reduce the activity of excitable cells via hyperpolarization. As such, they play a role in cardiac output, the coordination of movement and cognition. Due to their involvement in a multitude of pathways, the precision control of GIRK channels is an important endeavour. Here, we describe the development of the photoswitchable agonist (the ight perated IRK-channel pener), which activates GIRK channels in the dark and is rapidly deactivated upon exposure to long wavelength UV irradiation. is the first K channel opener and selectively targets channels that contain the GIRK1 subunit. It can be used to optically silence action potential firing in dissociated hippocampal neurons and exhibits activity , controlling the motility of zebrafish larvae in a light dependent fashion. We envisage that will be a valuable research tool to dissect the function of GIRK channels from other GPCR dependent signalling pathways.
G蛋白偶联内向整流钾通道（GIRKs）在人体中广泛表达，是抑制性信号转导通路的重要组成部分。当从G蛋白偶联受体（GPCRs）释放的G亚基结合时，GIRK通道打开，并通过超极化降低可兴奋细胞的活性。因此，它们在心脏输出、运动协调和认知中发挥作用。由于它们参与多种信号通路，对GIRK通道的精确控制是一项重要的工作。在这里，我们描述了光开关激动剂（光控IRK通道开放剂）的开发，它在黑暗中激活GIRK通道，并在暴露于长波长紫外线照射后迅速失活。它是首个钾通道开放剂，选择性靶向含有GIRK1亚基的通道。它可用于光学沉默离体海马神经元的动作电位发放，并表现出活性，以光依赖的方式控制斑马鱼幼虫的运动。我们设想，它将成为从其他GPCR依赖性信号通路中剖析GIRK通道功能的有价值的研究工具。
