ArticleThe Journal of general physiology2003
Molecular action of lidocaine on the voltage sensors of sodium channels.
Article in The Journal of general physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 114 citations in OpenAlex.
- Predicting Patient Response to the Antiarrhythmic Mexiletine Based on Genetic Variation.Circulation research · 2019Trial
- Oxaliplatin-induced peripheral neuropathy: from pathogenesis to treatment.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Review
- Efficacy of 10% lidocaine gel for injection site pain associated with treprostinil in the treatment of pulmonary hypertension: a report of four cases.JA clinical reports · 2025Article
- Modulation of Voltage-Gated Sodium Channels from Sensory Neurons by Isoeugenol.International journal of molecular sciences · 2025Article
- Drug distribution in dorsal root ganglion after peripheral application of Lidocaine patch.Scientific reports · 2025Article
- Eugenol and lidocaine inhibit voltage-gated NaFrontiers in pharmacology · 2024Article
- Topical Delivery Systems Effectively Transport Analgesics to Areas of Localized Pain via Direct Diffusion.Pharmaceutics · 2023Article
- Molecular Modeling of Cardiac Sodium Channel with Mexiletine.Membranes · 2022Article
- Sodium Channels and Local Anesthetics-Old Friends With New Perspectives.Frontiers in pharmacology · 2022Review
- Conformations of voltage-sensing domain III differentially define NaV channel closed- and open-state inactivation.The Journal of general physiology · 2021Review
- [Progress on the roles of glia in postoperative cognitive dysfunction].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2020Review
- Intracellular cardiomyocytes potential recording by planar electrode array and fibroblasts co-culturing on multi-modal CMOS chip.Biosensors & bioelectronics · 2019Article
- A Molecularly Detailed NaJACC. Basic to translational science · 2019Article
- Functional and Mechanistic Neurotoxicity Profiling Using Human iPSC-Derived Neural 3D Cultures.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Characterization of nAChRs inEvoDevo · 2019Article
- Propofol inhibits prokaryotic voltage-gated NaThe Journal of general physiology · 2018Article
- The Role of Neuroinflammation in Postoperative Cognitive Dysfunction: Moving From Hypothesis to Treatment.Frontiers in psychiatry · 2018Review
- Regulation of NaThe Journal of general physiology · 2017Article
- Localized neuropathic pain: an expert consensus on local treatments.Drug design, development and therapy · 2017Review
- Depolarization of the conductance-voltage relationship in the NaV1.5 mutant, E1784K, is due to altered fast inactivation.PloS one · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Block of sodium ionic current by lidocaine is associated with alteration of the gating charge-voltage (Q-V) relationship characterized by a 38% reduction in maximal gating charge (Q(max)) and by the appearance of additional gating charge at negative test potentials. We investigated the molecular basis of the lidocaine-induced reduction in cardiac Na channel-gating charge by sequentially neutralizing basic residues in each of the voltage sensors (S4 segments) in the four domains of the human heart Na channel (hH1a). By determining the relative reduction in the Q(max) of each mutant channel modified by lidocaine we identified those S4 segments that contributed to a reduction in gating charge. No interaction of lidocaine was found with the voltage sensors in domains I or II. The largest inhibition of charge movement was found for the S4 of domain III consistent with lidocaine completely inhibiting its movement. Protection experiments with intracellular MTSET (a charged sulfhydryl reagent) in a Na channel with the fourth outermost arginine in the S4 of domain III mutated to a cysteine demonstrated that lidocaine stabilized the S4 in domain III in a depolarized configuration. Lidocaine also partially inhibited movement of the S4 in domain IV, but lidocaine's most dramatic effect was to alter the voltage-dependent charge movement of the S4 in domain IV such that it accounted for the appearance of additional gating charge at potentials near -100 mV. These findings suggest that lidocaine's actions on Na channel gating charge result from allosteric coupling of the binding site(s) of lidocaine to the voltage sensors formed by the S4 segments in domains III and IV.
Indexed as
Identifiers
What OpenQuestion holds
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.