Channelrhodopsins are used widely for optical control of neurons, in which they generate photoinduced proton, sodium or chloride influx. Potassium (K) is central to neuron electrophysiology, yet no natural K-selective light-gated channel has been identified. Here, we report kalium channelrhodopsins (KCRs) from Hyphochytrium catenoides. Previously known gated potassium channels are mainly ligand- or voltage-gated and share a conserved K-selectivity filter. KCRs differ in that they are light-gated and have independently evolved an alternative K selectivity mechanism. The KCRs are potent, highly selective of K over Na, and open in less than 1 ms following photoactivation. The permeability ratio P/P of 23 makes H. catenoides KCR1 (HcKCR1) a powerful hyperpolarizing tool to suppress excitable cell firing upon illumination, demonstrated here in mouse cortical neurons. HcKCR1 enables optogenetic control of K gradients, which is promising for the study and potential treatment of potassium channelopathies such as epilepsy, Parkinson's disease and long-QT syndrome and other cardiac arrhythmias.
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http://dx.doi.org/10.1038/s41593-022-01094-6 | DOI Listing |
Nat Commun
January 2025
Shenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive.
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August 2024
Laboratory of Cell Fate Control, School of Life Sciences, Westlake University, Hangzhou, China.
Channelrhodopsins are popular optogenetic tools in neuroscience, but remain poorly understood mechanistically. Here we report the cryo-EM structures of channelrhodopsin-2 (ChR2) from Chlamydomonas reinhardtii and H. catenoides kalium channelrhodopsin (KCR1).
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July 2024
Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
Nat Commun
April 2024
Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
The analysis of neural circuits has been revolutionized by optogenetic methods. Light-gated chloride-conducting anion channelrhodopsins (ACRs)-recently emerged as powerful neuron inhibitors. For cells or sub-neuronal compartments with high intracellular chloride concentrations, however, a chloride conductance can have instead an activating effect.
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February 2024
Cell and Developmental Biology, University College London, London, WC1E 6BT UK.
Low-voltage fast (LVF) seizure-onset is one of the two frequently observed temporal lobe seizure-onset patterns. Depth electroencephalogram profile analysis illustrated that the peak amplitude of LVF onset was deep temporal areas, e.g.
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