Article
Neurosciences
Marina Arribas-Blazquez, Dolores Piniella, Luis A. Olivos-Ore, David Bartolome-Martin, Cristiana Leite, Cecilio Gimenez, Antonio R. Artalejo, Francisco Zafra
Summary: The voltage-sensitive sodium channel Na(V)1.1 is regulated by multiple protein kinases, with AKT1 identified as a novel regulator through direct phosphorylation. AKT1 activation leads to decreased Na+ currents and altered inactivation properties, mimicked by its specific activator SC79 and reverted by a selective inhibitor triciribine. This novel mechanism proposes AKT1 as a key regulator in modulating neuronal excitability under physiological and pathological conditions, including epileptogenesis.
Article
Biochemistry & Molecular Biology
Beata Niklas, Milena Jankowska, Dalia Gordon, Laszlo Beress, Maria Stankiewicz, Wieslaw Nowak
Summary: Animal venoms, particularly sea anemone polypeptides, affect neuronal electrical activity by targeting Nav channels. Different toxins exhibit varying potencies in increasing nerve activity, with partial overlap in binding modes between toxins and channels revealed through molecular docking. The higher neuronal activity observed in electrophysiology may be attributed to interactions between anemone toxins and the Nav channel's S4 helix.
Article
Biochemistry & Molecular Biology
Alican Gulsevin, Andrew M. Glazer, Tiffany Shields, Brett M. Kroncke, Dan M. Roden, Jens Meiler
Summary: This study identifies the binding site of veratridine (VTD) on the cardiac sodium ion channel (Na(V)1.5) using docking calculations and high-throughput electrophysiology experiments. The results suggest that VTD binds near the cytoplasmic mouth of the channel pore, potentially indicating an allosteric inactivation mechanism for VTD at Na(V)1.5.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Ena Ivanovic, Jan P. Kucera
Summary: Cardiac ephaptic coupling, mediated by negative electric potentials in intercalated discs, can be influenced by the convoluted structure of the discs. Concentric folds enhance ephaptic interactions, while radial folds attenuate ephaptic interactions.
Article
Neurosciences
Sidharth Tyagi, Nivedita Sarveswaran, Grant P. Higerd-Rusli, Shujun Liu, Fadia B. Dib-Hajj, Stephen G. Waxman, Sulayman D. Dib-Hajj
Summary: Non-addictive treatment for chronic pain is urgently needed. This study investigates the association between Rab6a and Na(V)1.7 and its impact on the trafficking of the channel, providing insights for potential therapeutic interventions.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Cardiac & Cardiovascular Systems
Madison B. Nowak, Steven Poelzing, Seth H. Weinberg
Summary: Cardiac action potentials are initiated by Na+ influx through Na+ channels, and GOF in these channels can lead to arrhythmias. Localization of cardiac Na+ channels at the intercalated disc facilitates EAD formation. Variability in cellular properties at different ages may lead to EADs presenting at early developmental stages.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Physiology
Carol J. Milligan, Lyndsey L. Anderson, Iain S. McGregor, Jonathon C. Arnold, Steven Petrou
Summary: Cannabis contains CBD and other phytocannabinoids with therapeutic potential for epilepsy. In this study, the effects of CBGA, CBDVA, CBG, CBCA, and CBC on human voltage-gated sodium channels were evaluated and compared to CBD. CBD and CBGA inhibited peak current amplitude, while CBG, CBCA, and CBC showed modest inhibition. CBDVA selectively inhibited Na(V)1.6.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Biology
Christian J. G. Tessier, Raymond M. Sturgeon, Johnathon R. Emlaw, Gregory D. McCluskey, F. Javier Perez-Areales, Corrie J. B. daCosta
Summary: Human adult muscle-type acetylcholine receptors are heteropentameric ion channels formed from different subunits, but they share a common ancestral homopentameric origin. A reconstructed ancestral muscle-type beta-subunit can form spontaneously open homopentameric ion channels, demonstrating that the function of the receptor is independent of agonist and does not require complex heteropentameric architecture.
Article
Multidisciplinary Sciences
Stephanie Cerceo Page, Srinidhi Rao Sripathy, Federica Farinelli, Zengyou Ye, Yanhong Wang, Daniel J. Hiler, Elizabeth A. Pattie, Claudia Nguyen, Madhavi Tippani, Rebecca L. Moses, Huei-Ying Chen, Matthew Nguyen Tran, Nicholas J. Eagles, Joshua M. Stolz, Joseph L. I. I. I. I. Catallini, Olivia R. Soudry, Dwight Dickinson, Karen F. Berman, Jose A. Apud, Daniel R. Weinberger, Keri Martinowich, Andrew E. Jaffe, Richard E. Straub, Brady J. Maher
Summary: The study analyzed neurons derived from individuals with high polygenic risk scores for schizophrenia (SCZ) and neurotypical individuals, finding that patient-derived neurons exhibited altered electrophysiological measures related to Na+ channel function, action potential interspike interval, and gamma-aminobutyric acid-ergic neurotransmission. These electrophysiological measures predicted core clinical and cognitive features in SCZ patients, potentially offering critical insights for novel therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Xinghua Feng, Jian Xiong, Weijie Cai, Jin-Bin Tian, Michael X. Zhu
Summary: This study revealed that the three OcTPCs form phosphoinositide-activated Na+ channels with different ligand selectivity, voltage dependence, and extracytosolic pH sensitivity. These findings provide important clues for further research and understanding of the function and regulation of these three two-pore channels.
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
Chemistry, Medicinal
Juan Antonio Contreras Vite, Carlos Vega Valle, Happi Biekeu Mbem, Sarah-Maude Boivin, Robert Dumaine
Summary: Lamotrigine is commonly used for treating bipolar disorder and epilepsy. The US FDA has recently issued a warning regarding the drug's potential to cause conduction anomalies and Brugada syndrome in epileptic patients. In this study, researchers used patch clamp technique on rat cardiomyocytes to investigate the effect of Lamotrigine on cardiac sodium current (I-Na). The results showed that Lamotrigine inhibited I-Na peak amplitude, reduced cardiac excitability, and prolonged the action potential refractory period in epileptic rats.
Article
Chemistry, Multidisciplinary
Shuaiwei Qi, Chenyang Zhang, Hao Yu, Jing Zhang, Tengfei Yan, Ze Lin, Bing Yang, Zeyuan Dong
Summary: Small molecules with natural channel-like functions have potential in treating human diseases. Aromatic helical scaffolds were used to develop foldamer-based ion channels of varying sizes, demonstrating the importance of channel size in ion transport selectivity and leading to the discovery of promising artificial K+ and sodiumpreferential channels.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Editorial Material
Dermatology
Theodora M. Mauro
Summary: The study demonstrated that skin sodium ion (Na+) is increased in patients with psoriasis, particularly those with a PASI > 5, and correlates with disease severity. The findings support a proposed mechanism where increased Na+ concentrations enhance IL-17 expression from CD4(+) cells. These results suggest a novel pathologic mechanism for psoriasis development and potential target for treatment.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Multidisciplinary Sciences
Federico Bertagna, Rebecca Lewis, S. Ravi P. Silva, Johnjoe McFadden, Kamalan Jeevaratnam
Summary: Research in recent decades has focused on the effects of different electromagnetic fields on the electrical properties of neurons, particularly voltage-gated ion channels. Changes in voltage-gated calcium channels have been found to be the most commonly reported result of electromagnetic field exposure. The effects of electromagnetic fields on the neuronal landscape appear to be diverse and highly dependent on factors such as the field's frequency, exposure time, and intrinsic properties of the irradiated tissue.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2021)
Article
Clinical Neurology
Rosie K. A. Bunton-Stasyshyn, Jacy L. Wagnon, Eric R. Wengert, Bryan S. Barker, Alexa Faulkner, Pravin K. Wagley, Kritika Bhatia, Julie M. Jones, Marissa R. Maniaci, Jack M. Parent, Howard P. Goodkin, Manoj K. Patel, Miriam H. Meisler
Editorial Material
Neurosciences
Michael A. Wheeler, Christopher D. Deppmann, Manoj K. Patel, Ali D. Guler
NATURE NEUROSCIENCE
(2020)
Article
Chemistry, Organic
Saurabh K. Tiwari, Km Neha Shivhare, Manoj K. Patel, Vikas Yadav, Mohd Nazeef, I. R. Siddiqui
Summary: We report an eco-friendly and facile strategy for the synthesis of 1,4-dihydropyridine (1,4-DHP) derivatives through a one pot multi-component Hantzsch reaction using glycerol as a promoting medium. The protocol offers a greener, economical, and expeditious synthesis of biologically significant 1,4-DHPs with moderate to excellent yields under metal-free mild reaction conditions. The additional advantages include operational simplicity, cost effectiveness, and reusability with the avoidance of hazardous volatile solvents.
POLYCYCLIC AROMATIC COMPOUNDS
(2022)
Article
Chemistry, Multidisciplinary
Manjula Singh, Laxmi Kant Sharma, Rahul Dubey, Manoj Kumar Patel, Ved Prakash, Rana Krishna Pal Singh
Article
Plant Sciences
Prince Saini, Shivani Bhatia, Monika Mahajan, Anshul Kaushik, Sangram Keshari Sahu, Asis Kumar, Santosh B. Satbhai, Manoj Kumar Patel, Shweta Saxena, Om Prakash Chaurasia, Maneesh Lingwan, Shyam Kumar Masakapalli, Ram Kishor Yadav
Article
Chemistry, Inorganic & Nuclear
Sikandar Paswan, Nitesh Jaiswal, Vishnu Kumar Modanawal, Manoj Kumar Patel, Rana Krishna Pal Singh
INORGANICA CHIMICA ACTA
(2020)
Review
Clinical Neurology
Eric R. Wengert, Manoj K. Patel
Summary: Voltage-gated sodium channels play a crucial role in generating action potentials in the nervous system, with a persistent sodium current contributing to normal neuronal function but potentially playing a pathogenic role in epilepsy. Targeting the persistent sodium current may hold promise for developing novel anti-seizure medication strategies.
Article
Clinical Neurology
Ian C. Wenker, Frida A. Teran, Eric R. Wengert, Pravin K. Wagley, Payal S. Panchal, Elizabeth A. Blizzard, Priyanka Saraf, Jacy L. Wagnon, Howard P. Goodkin, Miriam H. Meisler, George B. Richerson, Manoj K. Patel
Summary: The study revealed that apnea coincident with the tonic phase of a seizure, and subsequent failure to resume breathing, are determining events that cause seizure-induced death in Scn8a mutant mice.
ANNALS OF NEUROLOGY
(2021)
Article
Neurosciences
Eric R. Wengert, Ian C. Wenker, Elizabeth L. Wagner, Pravin K. Wagley, Ronald P. Gaykema, Jung-Bum Shin, Manoj K. Patel
Summary: This study demonstrates that mice harboring an Scn8a allele with a patient-derived mutation are susceptible to audiogenic seizures and seizure-induced death, providing a new model for studying seizure-induced death. Activation of adrenergic receptors is necessary and sufficient for recovery of breathing and prevention of seizure-induced death in this novel audiogenic seizure-induced death model.
FRONTIERS IN NEUROSCIENCE
(2021)
Editorial Material
Clinical Neurology
Eric R. Wengert, Manoj K. Patel
Article
Pharmacology & Pharmacy
Ankita Sharma, Shardulya Shukla, Abul Quasim, Manoj Kumar Patel, Raj Kumar, Om Prakash Chaurasia, Shweta Saxena
Summary: This study developed an in vitro regeneration protocol for Rubia cordifolia using nodal and leaf explants, and compared the phytochemical profiles of in vitro grown leaves (RUML) and roots (RUMR). The results showed that both leaves and roots contain medicinal compounds, with 8 compounds commonly present in both extracts.
ANNALS OF PHYTOMEDICINE-AN INTERNATIONAL JOURNAL
(2021)
Article
Engineering, Electrical & Electronic
Aarti Chauhan, Manoj Kumar Patel, Shilpa Chaudhary, Manoj Kumar Nayak, Surender Singh Saini, Pratap Pullammanappallil, Nadarajah Manivannan, Geoffrey Robert Mitchell, Wamadeva Balachandran
Summary: This research aims to evaluate the chargeability of sodium hypochlorite and an air-assisted electrostatic disinfection device. Five different surfaces were examined to assess efficacy, survival time, off-target losses, spray coverage, and disinfectant consumption. The results showed that sodium hypochlorite achieved a significant charge-to-mass ratio of 2.43 mC/kg at specific conditions and effectively eliminated Pseudomonas aeruginosa, Clostridium perfringens, and Bacteriophage MS2 colonies at a concentration of 1000 mg/L.
JOURNAL OF ELECTROSTATICS
(2023)
Article
Multidisciplinary Sciences
Aarti Chauhan, Manoj Kumar Patel, Manoj Kumar Nayak, Surender Singh Saini
Summary: Electrostatic spraying is an effective method for disinfecting surfaces to prevent transmission of SARS-CoV-2. The design and performance of a motorized pressure-nozzle based handheld electrostatic disinfection device were optimized, and the chargeability of various disinfectants was investigated.
Article
Agricultural Engineering
Yu Ru, Yangyang Liu, Rongjia Qu, Manoj Kumar Patel
INTERNATIONAL JOURNAL OF AGRICULTURAL AND BIOLOGICAL ENGINEERING
(2020)
Article
Engineering, Mechanical
Mayank Chouhan, Lalit Thakur, Dinesh Sindhu, Manoj K. Patel