ArticleThe Journal of biological chemistry2014
Modulation of the voltage-gated potassium channel (Kv4.3) and the auxiliary protein (KChIP3) interactions by the current activator NS5806.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Activation of TREK-1 and TREK-2 Two-Pore Domain Potassium Channels by the KPharmacology research & perspectives · 2026Article
- Pacemaking in the lymphatic system.The Journal of physiology · 2026Review
- Beyond the Alpha Subunit: Pharmacological Modulation of Kv4.2 Channels by Ancillary Proteins.Cells · 2026Review
- KCells · 2023Review
- Discovery of novel cardiac troponin activators using fluorescence polarization-based high throughput screening assays.Scientific reports · 2023Article
- Modulation of KInternational journal of molecular sciences · 2022Article
- Natural Mutations Affect Structure and Function of gC1q Domain of Otolin-1.International journal of molecular sciences · 2021Article
- Molecular mechanism of calcium induced trimerization of C1q-like domain of otolin-1 from human and zebrafish.Scientific reports · 2021Article
- Pharmacological Approaches for the Modulation of the Potassium Channel KInternational journal of molecular sciences · 2021Review
- Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets.Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- Increases in compulsivity, inflammation, and neural injury in HIV transgenic rats with escalated methamphetamine self-administration under extended-access conditions.Brain research · 2020Article
- Auxiliary subunits control biophysical properties and response to compound NS5806 of the Kv4 potassium channel complex.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Phase 1 repolarization rate defines CaThe Journal of general physiology · 2019Article
- Targeting the neuronal calcium sensor DREAM with small-molecules for Huntington's disease treatment.Scientific reports · 2019Article
- A polybasic motif in alternatively spliced KChIP2 isoforms prevents CaThe Journal of biological chemistry · 2019Article
- SUMOylating Two Distinct Sites on the A-type Potassium Channel, Kv4.2, Increases Surface Expression and Decreases Current Amplitude.Frontiers in molecular neuroscience · 2019Article
- Identification of IQM-266, a Novel DREAM Ligand That Modulates KFrontiers in molecular neuroscience · 2019Article
- Regulation of Kv4.3 and hERG potassium channels by KChIP2 isoforms and DPP6 and response to the dual KBiochemical pharmacology · 2018Article
- Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors.Channels (Austin, Tex.) · 2018Review
- KThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
KChIP3 (potassium channel interacting protein 3) is a calcium-binding protein that binds at the N terminus of the Kv4 voltage-gated potassium channel through interactions at two contact sites and has been shown to regulate potassium current gating kinetics as well as channel trafficking in cardiac and neuronal cells. Using fluorescence spectroscopy, isothermal calorimetry, and docking simulations we show that the novel potassium current activator, NS5806, binds at a hydrophobic site on the C terminus of KChIP3 in a calcium-dependent manner, with an equilibrium dissociation constant of 2-5 μM in the calcium-bound form. We further determined that the association between KChIP3 and the hydrophobic N terminus of Kv4.3 is calcium-dependent, with an equilibrium dissociation constant in the apo-state of 70 ± 3 μM and 2.7 ± 0.1 μM in the calcium-bound form. NS5806 increases the affinity between KChIP3 and the N terminus of Kv4.3 (Kd = 1.9 ± 0.1 μM) in the presence and absence of calcium. Mutation of Tyr-174 or Phe-218 on KChIP3 abolished the enhancement of Kv4.3 site 1 binding in the apo-state, highlighting the role of these residues in drug and K4.3 binding. Kinetic studies show that NS5806 decreases the rate of dissociation between KChIP3 and the N terminus of KV4.3. Overall, these studies support the idea that NS5806 directly interacts with KChIP3 and modulates the interactions between this calcium-binding protein and the T1 domain of the Kv4.3 channels through reorientation of helix 10 on KChIP3.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.