ArticleThe Journal of biological chemistry2009
Structural determinants of drugs acting on the Nav1.8 channel.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Differential state-dependent Nav1.8 inhibition by suzetrigine, LTGO-33, and A-887826.The Journal of general physiology · 2025Article
- Modulation of human dorsal root ganglion neuron firing by the Nav1.8 inhibitor suzetrigine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- State-Dependent Inhibition of Nav1.8 Sodium Channels by VX-150 and VX-548.Molecular pharmacology · 2024Article
- Use-Dependent Relief of Inhibition of Nav1.8 Channels by A-887826.Molecular pharmacology · 2023Article
- Structural basis for high-voltage activation and subtype-specific inhibition of human NaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Functional modulation of the human voltage-gated sodium channel NaChannels (Austin, Tex.) · 2021Article
- Status of peripheral sodium channel blockers for non-addictive pain treatment.Nature reviews. Neurology · 2020Review
- Conservation and divergence in NaChBac and NaScientific reports · 2020Article
- Mutagenesis of the NaChBac sodium channel discloses a functional role for a conserved S6 asparagine.European biophysics journal : EBJ · 2017Article
- Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.The Journal of general physiology · 2017Article
- A novel selective and orally bioavailable Nav 1.8 channel blocker, PF-01247324, attenuates nociception and sensory neuron excitability.British journal of pharmacology · 2015Article
- SCN10A/Nav1.8 modulation of peak and late sodium currents in patients with early onset atrial fibrillation.Cardiovascular research · 2014Article
- Small-fiber neuropathy Nav1.8 mutation shifts activation to hyperpolarized potentials and increases excitability of dorsal root ganglion neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Fast- or slow-inactivated state preference of Na+ channel inhibitors: a simulation and experimental study.PLoS computational biology · 2010Article
- Subtype-selective targeting of voltage-gated sodium channels.British journal of pharmacology · 2009Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The aim of this work is to study the role of pore residues on drug binding in the Na(V)1.8 channel. Alanine mutations were made in the S6 segments, chosen on the basis of their roles in other Na(V) subtypes; whole cell patch clamp recordings were made from mammalian ND7/23 cells. Mutations of some residues caused shifts in voltage dependence of activation and inactivation, and gave faster time course of inactivation, indicating that the residues mutated play important roles in both activation and inactivation in the Na(V)1.8 channel. The resting and inactivated state affinities of tetracaine for the channel were reduced by mutations I381A, F1710A, and Y1717A (for the latter only inactivated state affinity was measured), and by mutation F1710A for the Na(V)1.8-selective compound A-803467, showing the involvement of these residues for each compound, respectively. For both compounds, mutation L1410A caused the unexpected appearance of a complete resting block even at extremely low concentrations. Resting block of native channels by compound A-803467 could be partially removed ("disinhibition") by repetitive stimulation or by a test pulse after recovery from inactivation; the magnitude of the latter effect was increased for all the mutants studied. Tetracaine did not show this effect for native channels, but disinhibition was seen particularly for mutants L1410A and F1710A. The data suggest differing, but partially overlapping, areas of binding of A-803467 and tetracaine. Docking of the ligands into a three-dimensional model of the Na(V)1.8 channel gave interesting insight as to how the ligands may interact with pore residues.
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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.