Article
Neurosciences
Clement Verkest, Sylvie Diochot, Eric Lingueglia, Anne Baron
Summary: The study identifies JNK as a new post-translational positive regulator of ASICs in rodent sensory neurons, which can rapidly alter ASIC activity and contribute to peripheral sensitization and pain hypersensitivity.
JOURNAL OF NEUROSCIENCE
(2021)
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.
Article
Neurosciences
Surobhi Ganguly, Christopher H. Thompson, Alfred L. George
Summary: The recurrent SCN2A mutation R853Q leads to an overall loss-of-function, mainly due to an enhancement of slow inactivation. This mutation affects channel properties differently in neonatal and adult splice isoforms of the Na(V)1.2 channel, potentially explaining the later onset of neurological symptoms.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Neurosciences
Dmytro E. Duzhyy, Nana V. Voitenko, Pavel V. Belan
Summary: The study revealed that under peripheral inflammation conditions, the functional expression of acid-sensing ion channels and T-type Ca2+ channels in neurons increased, leading to enhanced neuronal excitability, which may contribute to chronic inflammatory pain.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Clinical Neurology
Chenyu Zhao, Jishuo Jin, Haoye Hu, Xi Zhou, Xiaoliu Shi
Summary: This study found that Scn11a(R222S/R222S) mice exhibited visceral hyperalgesia and intestinal dysmotility.
FRONTIERS IN NEUROLOGY
(2022)
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
Clinical Neurology
Christopher A. Hinckley, Zhonghua Zhu, Jen-hwa Chu, Cynthia Gubbels, Timm Danker, Jonathan J. Cherry, Christopher D. Whelan, Sandra J. Engle, Viet Nguyen
Summary: This study systematically examined various variants of the sodium-activated potassium channel KCNT1 and established their impact on channel function in multiple cellular systems. The most common six KCNT1 variants showed strong gain of function effects on one or more channel properties. Analysis of 36 total variants revealed phenotypic heterogeneity but a strong tendency for pathogenic variants to exert gain of function effects on channel properties.
Article
Anesthesiology
Christopher Marra, Timothy V. Hartke, Matthias Ringkamp, Mitchell Goldfarb
Summary: Transient voltage-gated sodium currents are regulated by FHFs, and the ablation of Fhf genes affects neurological and cardiac functions. Fhf2(null) mice exhibit cardiac conduction block and lack of heat nociception due to FHF2 deficiency and elevated temperature affecting the inactivation gating of sodium channels. This study explains the deficits in neurological and cardiac function in Fhf2(null) mice by the combined effects of FHF deficiency and temperature on sodium channel gating kinetics.
Article
Multidisciplinary Sciences
Qiong Wang, Jing Yang, Handong Wang, Bin Shan, Chengyu Yin, Hang Yu, Xuerou Zhang, Zishan Dong, Yulou Yu, Ran Zhao, Boyi Liu, Hailin Zhang, Chuan Wang
Summary: This study found that conditional knockout of Fgf13 in dorsal root ganglion (DRG) neurons attenuated pain responses induced by complete Freund's adjuvant (CFA). FGF13 was mainly expressed in small-diameter DRG neurons. CFA treatment increased FGF13 expression and excitability in nociceptive DRG neurons, which was inhibited in the absence of FGF13.
JOURNAL OF ADVANCED RESEARCH
(2021)
Article
Neurosciences
Ye Liu, Fang-Fang Zhang, Ying Song, Ran Wang, Qi Zhang, Zhong-Shan Shen, Fei-Fei Zhang, Dan-Ya Zhong, Xiao-Hui Wang, Qing Guo, Qiong-Yao Tang, Zhe Zhang
Summary: The Slack channel plays an important role in regulating mechanical pain-sensing, with high expression in specific neurons in the dorsal root ganglion and spinal cord.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Caixue Wang, Han Hao, Kaitong He, Yating An, Zeyao Pu, Nikita Gamper, Hailin Zhang, Xiaona Du
Summary: GABAergic inhibition in the peripheral sensory ganglia weakens during the development of neuropathic pain, but the alpha 5 subunit of the GABA(A) receptor may play a unique pro-algesic role in this process. Knock-down of the alpha 5 subunit alleviates neuropathic hyperalgesia, suggesting it could be a potential therapeutic target for neuropathic pain.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Physiology
Simon Loose, Annette Lischka, Samuel Kuehs, Carla Nau, Stefan H. Heinemann, Ingo Kurth, Enrico Leipold
Summary: This article reports a rare missense mutation in SCN10A gene, resulting in functional changes of the Na(V)1.8 channel, which is associated with abnormal thermoregulation, sensory abnormalities, and excessive sweating in the patient. Through current-clamp and voltage-clamp recordings, it was found that the mutation alters the voltage dependence of channel activation and inactivation, broadens the action potentials of sensory neurons, and increases their firing rates. Therefore, it is suggested that Na(V)1.8 p.V1287I variant has a gain-of-function effect at the cellular level and contributes to the patient's symptoms.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Neurosciences
Juan Sierra-Marquez, Jana Gehlen, Michael Schoeneck, Stefanie Bungert-Pluemke, Antje Willuweit, Carina Balduin, Frank Mueller, Angelika Lampert, Christoph Fahlke, Raul E. E. Guzman
Summary: ClC-3 modifies the electrical activity of peripheral nociceptors and is involved in inflammatory processes in the spinal cord. It regulates the number of ion channels in dorsal root ganglion neurons and is important for the homeostasis of glial cells. Reduced Cl-/H+ exchange contributes to inflammatory responses and affects neuronal excitability.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Oscar Brenes, Michael Pusch, Fernando Morales
Summary: Myotonia congenita is a hereditary muscle disease caused by mutations in the CLCN1 gene, leading to abnormal function of the chloride ion channel and resulting in muscle hyperexcitability and other symptoms. This review examines over 350 reported mutations and analyzes their effects on the structure and function of the chloride ion channel.
Article
Neurosciences
I-Shan Chen, Jodene Eldstrom, David Fedida, Yoshihiro Kubo
Summary: G-protein-gated inwardly rectifying K+ (GIRK; Kir3.x) channels play important roles in controlling cell excitation in various organs. Disease-associated mutations in these channels can lead to loss of K+ selectivity, with the G156S mutation showing a unique ion permeation pathway compared to other mutants.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Clinical Neurology
Bianca T. A. de Greef, Janneke G. J. Hoeijmakers, Margot Geerts, Mike Oakes, Tim J. E. Church, Stephen G. Waxman, Sulayman D. Dib-Hajj, Catharina G. Faber, Ingemar S. J. Merkies
Article
Neurosciences
Ivo Eijkenboom, Maurice Sopacua, Auke B. C. Otten, Monique M. Gerrits, Janneke G. J. Hoeijmakers, Stephen G. Waxman, Raffaella Lombardi, Giuseppe Lauria, Ingemar S. J. Merkies, Hubert J. M. Smeets, Catharina G. Faber, Jo M. Vanoevelen
EXPERIMENTAL NEUROLOGY
(2019)
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
Neurosciences
Malgorzata A. Mis, yang Yang, Brian S. Tanaka, Karolina Gomis-Perez, Shujun Liu, Fadia Dib-Hajj, Talia Adi, Rolando Garcia-Milian, Betsy R. Schulman, Sulayman D. Dib-Hajj, Stephen G. Waxman
JOURNAL OF NEUROSCIENCE
(2019)
Review
Pediatrics
Luke Arthur, Kirsty Keen, Madeleine Verriotis, Judy Peters, Alison Kelly, Richard F. Howard, Sulayman D. Dib-Hajj, Stephen G. Waxman, Suellen M. Walker
JOURNAL OF PEDIATRICS
(2019)
Review
Clinical Neurology
Maurice Sopacua, Janneke G. J. Hoeijmakers, Ingemar S. J. Merkies, Giuseppe Lauria, Stephen G. Waxman, Catharina G. Faber
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2019)
Review
Neurosciences
Sulayman D. Dib-Hajj, Stephen G. Waxman
ANNUAL REVIEW OF NEUROSCIENCE, VOL 42
(2019)
Editorial Material
Neurosciences
Stephen G. Waxman, Sulayman D. Dib-Hajj
Article
Neurosciences
Mathilde R. Israel, Brian S. Tanaka, Joel Castro, Panumart Thongyoo, Samuel D. Robinson, Peng Zhao, Jennifer R. Deuis, David J. Craik, Thomas Durek, Stuart M. Brierley, Stephen G. Waxman, Sulayman D. Dib-Hajj, Irina Vetter
JOURNAL OF PHYSIOLOGY-LONDON
(2019)
Article
Multidisciplinary Sciences
Zvonimir Vrselja, Stefano G. Daniele, John Silbereis, Francesca Talpo, Yury M. Morozov, Andre M. M. Sousa, Brian S. Tanaka, Mario Skarica, Mihovil Pletikos, Navjot Kaur, Zhen W. Zhuang, Zhao Liu, Rafeed Alkawadri, Albert J. Sinusas, Stephen R. Latham, Stephen G. Waxman, Nenad Sestan
Editorial Material
Anesthesiology
Stephen G. Waxman
Review
Anesthesiology
Stephen G. Waxman
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
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)