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Optical control of neuronal activity using a light-operated GIRK channel opener (LOGO)


Barber DMDavid M , Schönberger MMatthias , Burgstaller JJessica , Levitz JJoshua , Weaver CDC David , Isacoff EYEhud Y , Baier HHerwig , Trauner DDirk . Chemical science. 2015 11 23; 7(3). 2347-2352


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.