Article
Neurosciences
Dmytro V. Vasylyev, Shujun Liu, Stephen G. Waxman
Summary: We found that hyperpolarization-activated current (Ih) unexpectedly inhibits the activity of DRG neurons expressing WT Nav1.7, the largest inward current and primary driver of DRG neuronal firing, and hyperexcitable DRG neurons expressing a gain-of-function Nav1.7 mutation that causes IEM. Our results demonstrate that Ih increases the rheobase and reduces the firing probability in small DRG neurons, and reduces the amplitude of subthreshold oscillations. Ih has a damping action, which reverses from depolarizing to hyperpolarizing, close to the threshold for AP generation. Additionally, Ih reverses the hyperexcitability caused by a Nav1.7 mutation. These findings highlight the distinct effects of Ih in DRG neurons compared to cardiac cells.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Mathematics, Applied
Wei Yao, Yingchen Li, Zhihao Ou, Mingzhu Sun, Qiongxu Ma, Guanghong Ding
Summary: Acupuncture, as an important part of traditional Chinese medicine, has widely accepted efficacy, but its scientific basis is still lacking exploration. Some experimental studies have shown that acupuncture can alter cell membrane potential, thereby affecting nerve signal transmission. Based on theoretical models and numerical calculations, this paper proposes a hypothesis that mechanical stimulation can induce a current that leads to repeated discharge of cell membrane potential, and thus achieve analgesic effects.
MATHEMATICAL METHODS IN THE APPLIED SCIENCES
(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.
Article
Biology
Peter R. Strege, Luke M. Cowan, Constanza Alcaino, Amelia Mazzone, Christopher A. Ahern, Lorin S. Milescu, Gianrico Farrugia, Arthur Beyder
Summary: Shear stress and patch suction can reversibly alter the kinetic properties and maximum current of NaChBac, suggesting it is mechanosensitive. Structural analysis reveals a large displacement of the intracellular gate, supporting the proposed mechanosensitive mechanism.
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
Engineering, Mechanical
Dong Yu, Lijian Yang, Xuan Zhan, Ziying Fu, Ya Jia
Summary: In this work, a new method for designing logic circuits by mapping the output of a stochastic Hodgkin-Huxley neuron system to logic gate operations is reported. Logical stochastic resonance is achieved and low energy consumption is observed, indicating that HH neurons are excellent building blocks for logic circuits. The mechanisms underlying these findings are interpreted using bifurcation and phase plane diagrams. A neuronal network is constructed to improve the reliability of logic gates, where synaptic currents modulate the performance by regulating the switching time between steady states. Possible schemes for enhancing the reliability of logic gates are also discussed.
NONLINEAR DYNAMICS
(2023)
Article
Mathematics, Interdisciplinary Applications
Quan Xu, Yiteng Wang, Bei Chen, Ze Li, Ning Wang
Summary: This study proposes a memristive Hodgkin-Huxley circuit based on second-order and first-order local active memristors (LAMs) to simulate the complex nonlinearities of sodium and potassium ion channels, thus generating abundant spiking firing patterns. Numerical simulations and hardware experiments demonstrate the effectiveness of the circuit in generating periodic and chaotic spiking firing patterns.
CHAOS SOLITONS & FRACTALS
(2023)
Article
Biochemistry & Molecular Biology
Karl Josef Foehr, Michael Rapp, Michael Fauler, Thomas Zimmer, Bettina Jungwirth, David Alexander Christian Messerer
Summary: Aripiprazole has been identified as a potent blocker of the dominant voltage-gated sodium channel of heart muscle. Its interactions with the channel differ depending on the state, with weaker affinity for the resting state and stronger affinity for the inactivated state.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Pharmacology & Pharmacy
Peter Lukacs, Krisztina Pesti, Matyas C. Foldi, Katalin Zboray, Adam V. Toth, Gabor Papp, Arpad Mike
Summary: This study demonstrates a method for rapid assessment of the mechanism of action of sodium channel inhibitors using microfluidics-based automated patch clamp. By repeating a complex voltage protocol at 1 Hz, the researchers were able to monitor the onset and offset of channel block and modulation of gating upon drug perfusion and washout. The results show that the onset and offset of drug effects involve multiple steps on different time scales, and automated analysis allows for collection of detailed information regarding the mechanism of action of individual compounds.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Computer Science, Artificial Intelligence
Krishnendu Pal, Dibakar Ghosh, Gautam Gangopadhyay
Summary: In this study, a stochastic Langevin approach was used to investigate the role of channel noise in the kinetics and energetics of spiking of action potential and synchronization between neurons in a coupled Hodgkin-Huxley neuron system. Patch size was found to be crucial in synchronization and metabolic energy consumption, with exploration of postsynaptic neuron behavior in three different patch size ranges. The effects of sodium and potassium channel blockers on kinetic and energetic characteristics of synchronization and metabolic energy consumption rate were also discussed.
Article
Engineering, Biomedical
Tianlin Ying, Anthony N. Burkitt, Tatiana Kameneva
Summary: This study investigates the effects of extracellular potassium concentration and T-type calcium channel on epilepsy using microscopic and macroscopic models. The results show that increases in these factors can cause brain network transitions to pathological seizure-like dynamics within a limited range of network parameters. The slow-inhibitory synaptic gain has a stronger effect on network dynamics during transitions than the fast-inhibitory synaptic gain.
BIOMEDICAL SIGNAL PROCESSING AND CONTROL
(2023)
Article
Mathematics
Hu Wang, Sha Wang, Yajuan Gu, Yongguang Yu
Summary: This paper introduces a simplified two-dimensional Hodgkin-Huxley model that is exposed to electric fields. The study investigates the Hopf bifurcations of the simplified model through qualitative analysis and numerical simulations. The paper derives a necessary and sufficient condition for the existence of Hopf bifurcations and obtains the conditions for supercritical and subcritical Hopf bifurcations. Bifurcation diagrams are provided for two parameters, and numerical examples are used to demonstrate the efficacy of the theoretical results.
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
Mathematics, Applied
Yuanying Zhao, Changgui Gu, Huijie Yang
Summary: This study utilized graphlets to extract local temporal patterns and transitions in the output signals of neurons exposed to external stimuli. The transition-network structure was found to be influenced by stimulating periods, with the backbone size equaling the integer multiple. Interestingly, the structure within stimulating regions remained conservative, while the backbone or detailed structure significantly changed between different stimulating regions, primarily due to 12 active linkages.
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
Article
Neurosciences
Jianying Huang, Mark Estacion, Peng Zhao, Fadia B. Dib-Hajj, Betsy Schulman, Angela Abicht, Ingo Kurth, Knut Brockmann, Stephen G. Waxman, Sulayman D. Dib-Hajj
FRONTIERS IN NEUROSCIENCE
(2019)
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)
Article
Neurosciences
Matthew Alsaloum, Mark Estacion, Rowida Almomani, Monique M. Gerrits, Gidon J. Boenhof, Dan Ziegler, Rayaz Malik, Maryam Ferdousi, Giuseppe Lauria, Ingemar S. J. Merkies, Catharina G. Faber, Sulayman Dib-Hajj, Stephen G. Waxman, B. de Greef, J. G. J. Hoeijmakers, M. Sopacua, H. J. M. Smeets, J. M. Vanoevelen, I Eijkenboom, P. Lindsey, R. Almomani, M. Taiana, M. Marchi, R. Lombardi, D. Cazzato, F. M. Boneschi, A. Zauli, F. Clarelli, S. Santoro, I Lopez, A. Quattrini, S. Cestele, O. Chever, M. Tavakoli, R. Malik, D. Kapetis, M. N. Xenakis, M. Mantegazza, F. Battiato, A. Strom