Issue 3, 2016

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

Abstract

G-protein coupled inwardly rectifying potassium (GIRK) channels are expressed throughout the human body and are an integral part of inhibitory signal transduction pathways. Upon binding of Gβγ 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 LOGO (the Light-Operated GIRK channel Opener), which activates GIRK channels in the dark and is rapidly deactivated upon exposure to long wavelength UV irradiation. LOGO is the first photochromic 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 LOGO exhibits activity in vivo, controlling the motility of zebrafish larvae in a light-dependent fashion. We envisage that LOGO will be a valuable research tool to dissect the function of GIRK channels from other GPCR dependent signalling pathways.

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

Supplementary files

Article information

Article type
Edge Article
Submitted
27 Oct 2015
Accepted
01 Dec 2015
First published
23 Dec 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 2347-2352

Author version available

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

D. M. Barber, M. Schönberger, J. Burgstaller, J. Levitz, C. D. Weaver, E. Y. Isacoff, H. Baier and D. Trauner, Chem. Sci., 2016, 7, 2347 DOI: 10.1039/C5SC04084A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements