Article
Pharmacology & Pharmacy
Ivan Tochitsky, Sooyeon Jo, Nick Andrews, Masakazu Kotoda, Benjamin Doyle, Jaehoon Shim, Sebastien Talbot, David Roberson, Jinbo Lee, Louise Haste, Stephen M. Jordan, Bruce D. Levy, Bruce P. Bean, Clifford J. Woolf
Summary: BW-031 is a novel cationic sodium channel inhibitor that can be applied locally to inhibit inflammatory pain as well as effectively suppress cough in a guinea pig model of citric acid-induced cough.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Aurelie Fekete, Norbert Ankri, Romain Brette, Dominique Debanne
Summary: The distal shift of the axon initial segment (AIS) position increases axial resistance and excitability in L-5 pyramidal neurons, resulting in a decrease in the voltage threshold of the somatic action potential.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Rohit Pal, Bhupinder Kumar, Md. Jawaid Akhtar, Pooja A. Chawla
Summary: Voltage-gated sodium channel blockers are important targets for managing central nervous system diseases such as epilepsy, chronic pain, psychiatric disorders, and spasticity. These drugs work by reducing excitotoxicity and improving symptoms, with several new drugs in development to target abnormal neuronal excitability. Despite extensive research, there has been no groundbreaking discovery yet in controlling seizures through sodium channel blockers, and ongoing efforts are focused on developing more potent anticonvulsant drugs with minimized toxicity.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Clara M. Kerth, Petra Hautvast, Jannis Koerner, Angelika Lampert, Jannis E. Meents
Summary: This study reveals the functional change of the Nav1.7 p.I848T mutation causing inherited erythromelalgia, explaining the increase in voltage sensitivity through phosphorylation of the introduced Thr residue. Protein kinase C was identified as responsible for the phosphorylation of T848, altering channel function and potentially providing new treatment options for patients with chronic pain.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Neurosciences
Nivanthika K. Wimalasena, Daniel G. Taub, Jaehoon Shim, Sara Hakim, Riki Kawaguchi, Lubin Chen, Mahmoud El-Rifai, Daniel H. Geschwind, Sulayman D. Dib-Hajj, Stephen G. Waxman, Clifford J. Woolf
Summary: Mutations in the Scn9a gene can lead to various pain and neuropathy disorders. Previous studies have shown that the Nav1.7 gene mutation affects sodium conductance and neuronal excitability, but does not affect mechanical and thermal sensitivity in young mice. However, this new research demonstrates that as mice with this mutation age, they develop insensitivity to pain and cold, as well as skin lesions. Electrophysiology and RNA sequencing reveal a loss of sodium conductance and decreased expression of cLTMR genes in aged mice with the mutation.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Molly O'Reilly, Laura C. Sommerfeld, C. O'Shea, S. Broadway-Stringer, S. Andaleeb, J. S. Reyat, S. N. Kabir, D. Stastny, A. Malinova, D. Delbue, L. Fortmueller, K. Gehmlich, D. Pavlovic, B. Skryabin, A. P. Holmes, P. Kirchhof, L. Fabritz
Summary: This study found that the point mutation M1875T in the SCN5A gene is associated with familial AF. A new mouse model was used to show that this mutation causes gain-of-function of the cardiac sodium channel, resulting in increased atrial excitability.
Review
Dermatology
Haya S. Raef, Marta Williams, Flavia Fedeles
Summary: Erythromelalgia is a neurovascular disease that currently has no universally effective treatment. However, topical therapies can help alleviate symptoms.
DERMATOLOGIC THERAPY
(2022)
Article
Cell Biology
Yun Wu, Manyi Yang, Yubin Li, Wei Zhang, Maojun Zhou
Summary: Conotoxin Lt7b, a novel O-2-superfamily conotoxin, was synthesized and evaluated in this study. It was found that Lt7b could inhibit calcium currents, increase sodium currents, and had no obvious effects on potassium currents. Patch clamp experiments on ion channel subtypes showed that Lt7b could selectively inhibit certain types of currents. Furthermore, Lt7b exhibited no apparent toxicity to cells and increased the pain threshold in mice.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Lindsey Shapiro, Andrew Escayg, Jennifer C. Wong
Summary: Voltage-gated sodium channel genes are important for human epilepsy. SCN8A mutations can cause various clinical symptoms, including different types of seizures, movement disorders, intellectual disabilities, and autism. CBD treatment in RL/+ mutant mice showed dose-dependent seizure resistance and improved social behavior and reduced hyperactivity. CBD may be beneficial for patients with SCN8A-associated disease.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Yaping Xue, Melanie Kremer, Maria del Mar Muniz Moreno, Celeste Chidiac, Romain Lorentz, Marie-Christine Birling, Michel Barrot, Yann Herault, Claire Gaveriaux-Ruff
Summary: The SCN9A(R185H) mutation is found to be associated with chronic pain in patients with small fiber neuropathy (SFN). By establishing a mouse model, researchers discovered that the mutant mice have different pain sensitivity compared to wild-type mice. Bioinformatic analysis identified the factors contributing most to the pain phenotype. The study provides genetic evidence for the important role of this mutation in the Nav1.7 channel in nociception and pain experienced by SFN patients.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Qiurong Wu, Jian Huang, Xiao Fan, Kan Wang, Xueqin Jin, Gaoxingyu Huang, Jiaao Li, Xiaojing Pan, Nieng Yan
Summary: This article reports the high-resolution cryo-EM structures of human Na(v)1.7 bound to drugs and lead compounds, revealing the binding mode of these compounds on Na-v channels. The study demonstrates that different drugs can bind to different locations on the channel, providing a 3D structural map of known drug-binding sites.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Kiichi Takahashi, Takayoshi Ohba, Yosuke Okamoto, Atsuko Noguchi, Hiroko Okuda, Hatasu Kobayashi, Kouji H. Harada, Akio Koizumi, Kyoichi Ono, Tsutomu Takahashi
Summary: Inherited pain disorders can be caused by gain-of-function mutations in voltage-gated sodium channels like Na(V)1.7. A novel mutation (E44Q) in Na(V)1.7 was identified in a patient with paroxysmal pain attacks during childhood, and electrophysiological recordings showed that this mutation increased the amplitude of sodium current, indicating a gain-of-function effect. This study sheds light on the phenotypic spectrum and functional implications of Na(V)1.7 channelopathies.
Article
Biochemistry & Molecular Biology
Jiangtao Zhang, Yiqiang Shi, Zhuo Huang, Yue Li, Bei Yang, Jianke Gong, Daohua Jiang
Summary: This study reports the cryo-EM structures of Na(V)1.7 in complexes with three pore blockers, elucidating the mechanisms of their modulation on Na(V)1.7. The findings have important implications for developing subtype-selective analgesics.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Dermatology
Andrea Michelerio, Carlo Tomasini, Eloisa Arbustini, Camilla Vassallo
Summary: This study investigated the characteristics, gene mutations, and treatment efficacy of patients with primary erythromelalgia (EM), and proposed a diagnostic algorithm. The results showed that the diagnosis and treatment of EM are challenging, with patients displaying varied clinical manifestations and severity. The most effective therapies were antihistamines, venlafaxine, and mexiletine.
DERMATOLOGY PRACTICAL & CONCEPTUAL
(2023)
Article
Biochemistry & Molecular Biology
Rama A. Hussein, Marwa Ahmed, Stefan H. Heinemann
Summary: Selenomethionine (SeMet) readily replaces methionine (Met) residues in proteins during translation, but little is known about its effect on electrical excitability and ion channels. SeMet mis-incorporation sensitizes voltage-gated sodium (NaV) channels to oxidative stress, resulting in loss of inactivation and diminished current.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Clinical Neurology
Ivo Eijkenboom, Maurice Sopacua, Janneke G. J. Hoeijmakers, Bianca T. A. de Greef, Patrick Lindsey, Rowida Almomani, Margherita Marchi, Jo Vanoevelen, Hubertus J. M. Smeets, Stephen G. Waxman, Giuseppe Lauria, Ingemar S. J. Merkies, Catharina G. Faber, Monique M. Gerrits
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2019)
Article
Pharmacology & Pharmacy
Hong Joon Lee, Bok Hee Choi, Jin-Sung Choi, Sang June Hahn
EUROPEAN JOURNAL OF PHARMACOLOGY
(2019)
Article
Pharmacology & Pharmacy
Dong-Hyun Kim, Kang-Sik Park, See-Hyoung Park, Sang June Hahn, Jin-Sung Choi
EUROPEAN JOURNAL OF PHARMACOLOGY
(2020)
Review
Neurosciences
Xiaoyang Cheng, Jin-Sung Choi, Stephen G. Waxman, Sulayman D. Dib-Hajj
Summary: Peripheral neuropathy is associated with enhanced activity of primary afferents which is often manifested as pain. Voltage-gated sodium channels (VGSCs) are critical for the initiation and propagation of action potentials. Distinct biophysical properties of different VGSCs contribute to finely tuned neuronal firing in nociceptors, and mutations in these channels can lead to inherited pain disorders. Inflammatory response triggered by peripheral tissue damage can modulate expression and activity of ion channels, including VGSCs, contributing to the development and maintenance of pathological pain conditions. This review discusses the signaling pathways activated by pro-nociceptive inflammatory mediators that regulate peripheral sodium channels and focuses on direct phosphorylation of these channels by multiple protein kinases.
NEUROSCIENCE LETTERS
(2021)
Article
Neurosciences
Hong Joon Lee, Bok Hee Choi, Jin-Sung Choi, Sang June Hahn
Summary: Iloperidone concentration-dependently inhibited hERG 1A/3.1 currents by preferentially interacting with the open states of channels, rather than by disrupting membrane trafficking or surface membrane expression of channel proteins.
Article
Chemistry, Medicinal
Juhee Park, Ga-Eun Lee, Hyung-Jung An, Cheol-Jung Lee, Eun Suh Cho, Han Chang Kang, Joo Young Lee, Hye Suk Lee, Jin-Sung Choi, Dae Joon Kim, Jong-Soon Choi, Yong-Yeon Cho
Summary: Kaempferol targeting RSKs may be a strategy to reduce oxaliplatin-resistant colon cancer cells. The study provides evidence that molecular mechanisms for drug resistance in human cancer are crucial in overcoming this challenge.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Hyun-Jung An, Cheol-Jung Lee, Ga-Eun Lee, Youngwon Choi, Dohyun Jeung, Weidong Chen, Hye Suk Lee, Han Chang Kang, Joo Young Lee, Dae Joon Kim, Jin-Sung Choi, Eun Suh Cho, Jong-Soon Choi, Yong-Yeon Cho
Summary: FBXW7 regulates ERK3 stability by promoting its ubiquitination and degradation, thereby suppressing lung cancer cell proliferation.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Chemistry, Medicinal
Ga-Eun Lee, Dohyun Jeung, Weidong Chen, Jiin Byun, Joo Young Lee, Han Chang Kang, Hye Suk Lee, Dae Joon Kim, Jin-Sung Choi, Cheol-Jung Lee, Hyun-Jung An, Yong-Yeon Cho
Summary: In this study, it was found that FBXO1 binds to E2Fs and induces ubiquitination and degradation of E2Fs. The residues Arg/Ile and R/Val in the dimerization domain of E2Fs act as degron motifs for FBXO1. MEK/ERK signaling molecules play a key role in the interaction between FBXO1 and E2Fs and modulate E2F protein turnover. Modulating the stability of E2Fs through the FBXO1-E2Fs axis can delay G(1)/S cell cycle transition and inhibit cancer cell proliferation.
ARCHIVES OF PHARMACAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Milena Sleczkowska, Rowida Almomani, Margherita Marchi, Erika Salvi, Bianca T. A. de Greef, Maurice Sopacua, Janneke G. J. Hoeijmakers, Patrick Lindsey, Stephen G. Waxman, Giuseppe Lauria, Catharina G. Faber, Hubert J. M. Smeets, Monique M. Gerrits
Summary: This study assessed the role of fifteen ion channel genes in neuropathic pain. Variants in ion channel genes were identified in SFN patients, with TRP genes being the most frequent. Patients with these variants reported more severe pain. This study provides promising gene candidates for future research on neuropathic pain etiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jeong-hee Choi, Ryeong-Eun Kim, Yong-Yeon Cho, Jin-Sung Choi
Summary: In order to test the cardiac safety of antiarrhythmic drugs, a stable HEK293 cell line expressing hNav1.5 channels was established. The effects of lidocaine on this cell line were examined using both conventional and automated patch-clamp systems. Lidocaine blocked hNav1.5 currents in a concentration- and voltage-dependent manner.
MOLECULAR & CELLULAR TOXICOLOGY
(2023)
Article
Neurosciences
Ryeong-Eun Kim, Jin-Sung Choi
Summary: Polysorbate 80 is a widely used emulsifier derived from polyethoxylated sorbitan and oleic acid. It has been found to inhibit the Na(v)1.7 sodium channel current in a concentration-, state-, and use-dependent manner. This suggests that polysorbate 80 may be helpful in pain medicine as an excipient, but caution should be taken in conducting in vitro experiments with neurons using polysorbate 80.
Article
Biochemistry & Molecular Biology
Chan-Su Bok, Ryeong-Eun Kim, Yong-Yeon Cho, Jin-Sung Choi
Summary: This study investigated the blocking effects of tramadol on sodium currents in HEK293 cells expressing Nav1.7 and Nav1.5 channels. Tramadol inhibited both channels with IC50 values of 0.73 mM and 0.43 mM, respectively. Tramadol also shifted the steady-state inactivation curves, slowed the recovery rate, and induced stronger use-dependent inhibition. The plasma concentration of tramadol upon oral administration is unlikely to block Nav1.7 or Nav1.5 effectively, but it may act as a local anesthetic or antiarrhythmic agent at high concentrations by injection.
BIOMOLECULES & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Rowida Almomani, Maurice Sopacua, Margherita Marchi, Milena Sleczkowska, Patrick Lindsey, Bianca T. A. de Greef, Janneke G. J. Hoeijmakers, Erika Salvi, Ingemar S. J. Merkies, Maryam A. Ferdousi, Rayaz Malik, Dan Ziegler, Kasper W. J. Derks, Gidon Boenhof, Filippo Martinelli-Boneschi, Daniele Cazzato, Raffaella Lombardi, Sulayman G. Dib-Hajj, Stephen Waxman, Hubert J. M. M. Smeets, Monique G. Gerrits, Catharina Faber, Giuseppe Lauria
Summary: Rare SCG genetic variants may contribute to the development of painful neuropathy. Genetic profiling and SCG variant identification can provide better understanding of the genetic variability in patients with painful and painless neuropathy, leading to improved risk stratification and personalized pain treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Spectroscopy
Jin-Sung Choi, Hye Suk Lee
Summary: Amatoxin-induced mushroom poisoning can lead to liver damage, liver insufficiency, and even death. Accurate detection of amatoxins within the first few hours after symptoms appear is crucial for improving therapeutic outcomes. This literature review explores the analytical techniques, such as liquid chromatography combined with mass spectrometry, ultraviolet detection, and electrochemical detection, that are necessary for clinical and forensic toxicology.
MASS SPECTROMETRY LETTERS
(2022)
Article
Pharmacology & Pharmacy
Jeaneun Park, Kwang-Hyun Cho, Hong Joon Lee, Jin-Sung Choi, Duck-Joo Rhie
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
(2020)