ArticleScientific reports2016
Remote and reversible inhibition of neurons and circuits by small molecule induced potassium channel stabilization.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Conserved Kir channel mechanisms governing intrinsic excitability in human and rodent parvalbumin neurons.Communications biology · 2026Article
- Chemically-inducible CRISPR/Cas9 circuits for ultra-high dynamic range gene perturbation.Nature communications · 2025Article
- Dissecting mammalian cortical circuit development at single-cell resolution using inducible barcoded rabies virus.bioRxiv : the preprint server for biology · 2025Article
- Regulation of input excitability in human and mouse parvalbumin interneurons by Kir potassium channels.bioRxiv : the preprint server for biology · 2025Article
- Development of covalent chemogenetic KCell chemical biology · 2024Article
- Destabilized reporters for background-subtracted, chemically-gated, and multiplexed deep-tissue imaging.Chemical science · 2024Article
- Protein-Based Tools for Studying Neuromodulation.ACS chemical biology · 2024Review
- Article
- Development of covalent chemogenetic KbioRxiv : the preprint server for biology · 2023Article
- Protease-controlled secretion and display of intercellular signals.Nature communications · 2022Article
- Targeted Protein Degradation by Small Molecules.Annual review of pharmacology and toxicology · 2017Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Manipulating the function of neurons and circuits that translate electrical and chemical signals into behavior represents a major challenges in neuroscience. In addition to optogenetic methods using light-activatable channels, pharmacogenetic methods with ligand induced modulation of cell signaling and excitability have been developed. However, they are largely based on ectopic expression of exogenous or chimera proteins. Now, we describe the remote and reversible expression of a Kir2.1 type potassium channel using the chemogenetic technique of small molecule induced protein stabilization. Based on shield1-mediated shedding of a destabilizing domain fused to a protein of interest and inhibition of protein degradation, this principle has been adopted for biomedicine, but not in neuroscience so far. Here, we apply this chemogenetic approach in brain research for the first time in order to control a potassium channel in a remote and reversible manner. We could show that shield1-mediated ectopic Kir2.1 stabilization induces neuronal silencing in vitro and in vivo in the mouse brain. We also validated this novel pharmacogenetic method in different neurobehavioral paradigms.The DD-Kir2.1 may complement the existing portfolio of pharmaco- and optogenetic techniques for specific neuron manipulation, but it may also provide an example for future applications of this principle in neuroscience research.
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