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| Open AccessThe Ca2+-activated chloride channel anoctamin-2 mediates spike-frequency adaptation and regulates sensory transmission in thalamocortical neurons
Spike-frequency adaptation in thalamocortical (TC) neurons is important for sensory transmission though the underlying mechanisms are not fully understood. Here, the authors identify a role for the calcium-activated chloride channel, ANO2, in mediating TC spiking adaptations and visceral pain response.
- Go Eun Ha
- , Jaekwang Lee
- & Eunji Cheong
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| Open AccessASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion
The acid-sensing ion channel, ASIC1a, is known to play a role in synaptic transmission and plasticity. Here, the authors demonstrate a role for ASIC1a in regulating plasticity in the insular cortex and find that extinction of conditioned taste aversion memory is disrupted in the ASIC1a knockout mice.
- Wei-Guang Li
- , Ming-Gang Liu
- & Tian-Le Xu
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| Open AccessRegulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitability
It is not clear how circadian biochemical cascades are encoded into neural electrical signals. Here, using a combination of electrophysiology and modelling approaches in mice, the authors show activation of glycogen synthase kinase 3 modulates neural activity in the suprachiasmatic nuclei via regulation of the persistent sodium current, INaP.
- Jodi R. Paul
- , Daniel DeWoskin
- & Karen L. Gamble
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| Open AccessKCNE1 induces fenestration in the Kv7.1/KCNE1 channel complex that allows for highly specific pharmacological targeting
Specificity of inhibitors of voltage-gated ion channels is crucial for their use as therapeutics. Here, the authors show that adamantane derivatives interact with a specific binding site on fenestrations that only become available when accessory subunits are bound to the channel.
- Eva Wrobel
- , Ina Rothenberg
- & Guiscard Seebohm
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Article
| Open AccessNicotinamide is an endogenous agonist for a C. elegans TRPV OSM-9 and OCR-4 channel
TRPV are cation channels activated by physical and chemical stimuli. Here the authors show that nicotinamide is a soluble, endogenous agonist for orthologous TRPV channels fromC. elegans and Drosophila, unveiling a metabolic-based regulation for TRPV channel activity.
- Awani Upadhyay
- , Aditya Pisupati
- & Wendy Hanna-Rose
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| Open AccessLocalized force application reveals mechanically sensitive domains of Piezo1
Piezo ion channels transduce mechanical forces into biological signals. Here, the authors use magnetic tweezers to pull specific regions of Piezo1, identifying mechanically sensitive domains that are essential for channel activation and inactivation.
- Jason Wu
- , Raman Goyal
- & Jörg Grandl
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Article
| Open AccessFHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon
FHFs are known to regulate voltage-gated sodium channels (NaVs). Here, the authors compare the role of FHFs in cerebellar granule cell propagation, and find NaVs in the distal axon function independently of FHFs, allowing for faster inactivation rates and reducing energy demands during repetitive spiking.
- Katarzyna Dover
- , Christopher Marra
- & Mitchell Goldfarb
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| Open AccessEvidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors
Acid-sensing ion channel 3 (ASIC3) is known to play a role in nociception, but its role in low threshold neurosensory mechanotransduction is unclear. Here, the authors target ASIC3 expression in dorsal root ganglion parvalbumin positive neurons and find ASIC3 contributes to dynamic proprioception responses.
- Shing-Hong Lin
- , Yuan-Ren Cheng
- & Chih-Cheng Chen
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| Open AccessKv3.1 uses a timely resurgent K+ current to secure action potential repolarization
Kv3 potassium channels have an important role in the repolarization of action potentials in fast-spiking neurons. Here, the authors use electrophysiology and modelling to report on an interesting mechanism that might explain their gating behaviour.
- Alain J. Labro
- , Michael F. Priest
- & Francisco Bezanilla
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| Open AccessA pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1
The venom of the Chinese red-headed centipede causes excruciating pain. Here, Yanget al. identify a novel toxin protein from the centipede venom and find that it can activate the nociceptive TRPV1 ion channel by binding to the channel’s outer pore to potentiate the heat activation machinery.
- Shilong Yang
- , Fan Yang
- & Ren Lai
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Coordination and fine motor control depend on Drosophila TRPγ
Perception of mechanical tension is important for coordinated locomotion, and in Drosophila, mutations in stretch-sensitive TRPV channels grossly impair locomotor behaviour. Akitake et al. show that the Drosophila TRPC channel TRPγis, in contrast, specifically required for fine motor control.
- Bradley Akitake
- , Qiuting Ren
- & Craig Montell
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| Open AccessPiezo1 ion channel pore properties are dictated by C-terminal region
Piezo ion channels function as mechanotransducers involved in vascular development and touch sensing, but their structural features remain unknown. Here the authors find that the C-terminal region of Piezo protein encompasses the pore and identify a glutamate residue within this region involved in ion conduction properties.
- Bertrand Coste
- , Swetha E. Murthy
- & Ardem Patapoutian
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| Open AccessPhotoswitchable fatty acids enable optical control of TRPV1
Fatty acids are ancient lipids with numerous functions, from metabolic processes as a source of energy to structural and signalling roles within cell membranes. Here, the authors present azobenzene-modified fatty acids and their application as photoswitchable agonists of the Vanilloid Receptor 1.
- James Allen Frank
- , Mirko Moroni
- & Dirk Trauner
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KCNQ5 K+ channels control hippocampal synaptic inhibition and fast network oscillations
Several K+ channels control neuronal excitability, but the function of KCNQ5 (Kv7.5), which displays wide expression in the brain, is not known. Here the authors show that KCNQ5 controls excitability and function of hippocampal networks through modulation of synaptic inhibition.
- Pawel Fidzinski
- , Tatiana Korotkova
- & Thomas J. Jentsch
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Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools
Efforts to improve the performance of optogenetic tools for neuroscience research have mostly been focused on mutating the opsin backbones or mining-related algal genomes. Here the authors show that analogues of the chromophore, retinal, can be used for colour tuning of rhodopsins and altering their photocycle kinetics in several model organisms.
- N. AzimiHashemi
- , K. Erbguth
- & J. F. Liewald
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Diacylglycerol mediates regulation of TASK potassium channels by Gq-coupled receptors
TASK-1 and -3 are members of the two-pore domain K+ channel family that play important roles in the regulation of cellular excitability. Here, Wilke et al.demonstrate that the second messenger lipid diacylglycerol (DAG) gates TASK1/3, defining a new role for DAG in controlling the dynamics of cellular excitability.
- Bettina U. Wilke
- , Moritz Lindner
- & Dominik Oliver
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Singular localization of sodium channel β4 subunit in unmyelinated fibres and its role in the striatum
Voltage-gated Na+ channel β-subunits are concentrated in the nodes of Ranvier and axon initial segments of myelinated axons and have a variety of functions. Here the authors show, using genetically modified mice, that this subunit is present in unmyelinated fibres in the striatum and is required for generation of resurgent Na+ current in striatal neurons.
- Haruko Miyazaki
- , Fumitaka Oyama
- & Nobuyuki Nukina
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A non-inactivating high-voltage-activated two-pore Na+ channel that supports ultra-long action potentials and membrane bistability
Our understanding of the function and molecular origin of ultra-long action potentials—which can last a few seconds to several minutes—is extremely limited. Here, Cang et al. show that ultra-long action potentials are generated by a novel type of voltage-gated sodium channel.
- Chunlei Cang
- , Kimberly Aranda
- & Dejian Ren
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Enhancing the fidelity of neurotransmission by activity-dependent facilitation of presynaptic potassium currents
It remains unclear how nerve terminals sustain neurotransmitter release during intense activity. Yang et al. show that, in the calyx of Held, the retention of K+ channels in intermediate gating states between high-frequency spikes controls synaptic vesicle release by constraining presynaptic Ca2+influx.
- Yi-Mei Yang
- , Wei Wang
- & Lu-Yang Wang
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A fully genetically encoded protein architecture for optical control of peptide ligand concentration
The design of optogenetic tools to control ion channel function typically requires careful consideration of channel structure. Schmidt et al. present a modular strategy to engineer light sensitivity in several K+channels, which functions independently of exogenous chemical modulators.
- Daniel Schmidt
- , Paul W. Tillberg
- & Edward S. Boyden
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Activation of TREK-1 by morphine results in analgesia without adverse side effects
Opioid analgesic drugs act at opioid receptors to exert analgesic effects, but they also exert adverse side effects. In this study, the authors show that the TREK-1 potassium channel is responsible for mediating the analgesic effects of morphine but not the adverse side effects.
- Maïly Devilliers
- , Jérôme Busserolles
- & Alain Eschalier
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A modern ionotropic glutamate receptor with a K+ selectivity signature sequence
Glutamate is the major excitatory neurotransmitter in the mammalian nervous system. Here, a glutamate receptor is reported that has properties intermediate to those of bacterial and eukaryotic glutamate-gated ion channels, suggesting a link in the evolution of ionotropic glutamate receptors.
- H. Janovjak
- , G. Sandoz
- & E. Y. Isacoff