Lookup NU author(s): Dr Hannah Alfonsa,
Professor Jeremy Lakey,
Professor Robert Lightowlers,
Professor Andrew Trevelyan
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Chloride regulation affects brain function in many ways, for instance, by dictating the GABAergic reversal potential, and thereby influencing neuronal excitability and spike timing. Consistent with this, there is increasing evidence implicating chloride in a range of neurological conditions. Investigations about these conditions, though, are made difficult by the limited range of tools available to manipulate chloride levels. In particular, there has been no way to actively remove chloride from neurons; we now describe an optogenetic strategy, 'Cl- out', to do exactly this. Cl-out achieves its effect by the cooperative action of two different component opsins: the proton pump, Archaerhodopsin and a chloride channel opsin. The removal of chloride happens when both are activated together, using Archaerhodopsin as an optical voltage clamp to provide the driving force for chloride removal through the concurrently opened, chloride channels. We further show that this novel optogenetic strategy can reverse an in vitro epileptogenic phenotype.
Author(s): Alfonsa H, Lakey JH, Lightowlers RN, Trevelyan AJ
Publication type: Article
Publication status: Published
Journal: Nature Communications
Online publication date: 17/11/2016
Acceptance date: 10/10/2016
Date deposited: 19/01/2017
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
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