Article
Neurosciences
Akira Kawanabe, Kohei Takeshita, Maki Takata, Yuichiro Fujiwara
Summary: ATP is important for maintaining the activity of the voltage-gated proton channel (Hv1) through direct molecular interactions. It accelerates the activation kinetics of Hv1, leading to an increase in proton current. The physiological regulation of Hv1 activity relies on the presence of cytosolic ATP.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Review
Biochemistry & Molecular Biology
Silvia Cassinelli, Carla Vinola-Renart, Anna Benavente-Garcia, Maria Navarro-Perez, Jesusa Capera, Antonio Felipe
Summary: Protein lipidation is a common form of posttranslational modification that regulates various aspects of a protein's physiology, including its structure, stability, and interaction with cellular membranes. Palmitoylation, the addition of long saturated fatty acid chains to proteins, is a key form of lipidation. Enzymes called acyltransferases and thioesterases control the behavior of palmitoylated proteins through a series of acylation and deacylation cycles. Palmitoylation plays a pleiotropic role in regulating the trafficking, spatial organization, and electrophysiological properties of ion channels, particularly voltage-gated ion channels (VGICs). Dysregulation of palmitoylation in VGICs and associated subunits is linked to the development of diseases such as cancer and mental disorders. Therefore, protein palmitoylation is emerging as an important factor in cellular protein regulation and human health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Clifford TeBay, Jeffrey R. McArthur, Melissa Mangala, Nicholas Kerr, Stewart Heitmann, Matthew D. Perry, Monique J. Windley, Jamie Vandenberg, Adam P. Hill
Summary: Hydroxychloroquine, chloroquine, and azithromycin have been proposed as drugs to treat COVID-19, but they carry a risk of proarrhythmia. Factors such as electrolyte imbalances, acidosis, and temperature can alter the potency of these drugs and increase the risk of proarrhythmia. In vitro screening and in silico simulations can help guide the preclinical screening and clinical management of patients receiving these drugs.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Physiology
Balazs Horvath, Norbert Szentandrassy, Csaba Dienes, Zsigmond M. Kovacs, Peter P. Nanasi, Ye Chen-Izu, Leighton T. Izu, Tamas Banyasz
Summary: The patch clamp technique has undergone continuous advancement in cardiac electrophysiology, allowing for the recording of multiple currents under various command pulses. Its potential applications in integrative physiology are highlighted in this review.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Valerij S. Sokolov, Vladimir V. Cherny, Artem G. Ayuyan, Thomas E. DeCoursey
Summary: H(V)1 channels, resembling the voltage-sensing domain of other voltage-gated ion channels, feature a unique Delta pH dependent gating mechanism that regulates channel opening by pH on both sides of the membrane. Two mechanisms, the countercharge mechanism and the electrostatic mechanism, are proposed to contribute to this Delta pH dependent gating. Both mechanisms are likely to operate together to regulate the gating of H(V)1 channels.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Article
Biochemistry & Molecular Biology
Noelia Rodriguez Araujo, Guillermina Hernando, Jeremias Corradi, Cecilia Bouzat
Summary: This study reveals the potential compounds regulating the function of MOD-1 and demonstrates its role in worm locomotion, suggesting MOD-1 as a potential target for anthelmintic therapy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Biology
Timothy J. Baumgartner, Zahra Haghighijoo, Nana A. Goode, Nolan M. Dvorak, Parsa Arman, Fernanda Laezza
Summary: Alzheimer's disease is characterized by two major histopathological abnormalities: extracellular plaques composed of amyloid beta and intracellular hyperphosphorylated tau. Attenuation of hippocampal hyperactivity, which is linked to dysfunction of voltage-gated Na+ channels, has emerged as a promising therapeutic strategy for early-stage AD. This review explores the role of Nav channels in neuronal function, their connections to AD pathology, and their potential as therapeutic targets.
Review
Physiology
Mohammad-Reza Ghovanloo, Sulayman D. Dib-Hajj, Samuel J. Goodchild, Peter C. Ruben, Stephen G. Waxman
Summary: Phytocannabinoids, such as CBD and CBG, interact with Nav channels and may have therapeutic effects, especially in treating conditions like pain.
FRONTIERS IN PHYSIOLOGY
(2022)
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
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.
Review
Health Care Sciences & Services
Grace Hey, Rohan Rao, Ashley Carter, Akshay Reddy, Daisy Valle, Anjali Patel, Drashti Patel, Brandon Lucke-Wold, Daniel Pomeranz Krummel, Soma Sengupta
Summary: Gliomas are aggressive and heterogeneous primary brain malignancies that are difficult to treat. Ligand-gated ion channels (LGICs) have been identified as valuable biomarkers and diagnostic tools in the pathogenesis of gliomas. Various LGICs, including P2X, SYT16, and PANX2, can be altered in glioma, disrupting neural homeostasis and worsening symptoms. LGICs, such as purinoceptors, glutamate-gated receptors, and Cys-loop receptors, are being targeted in clinical trials for potential therapeutic benefits in glioma diagnosis and treatment.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Multidisciplinary Sciences
Kazuki Okamoto, Teppei Ebina, Naoki Fujii, Kuniaki Konishi, Yu Sato, Tetsuhiko Kashima, Risako Nakano, Hiroyuki Hioki, Haruki Takeuchi, Junji Yumoto, Masanori Matsuzaki, Yuji Ikegaya
Summary: The newly introduced Tb3+-doped glass material emits green fluorescence in biological experiments and is compatible with conventional research environments. Using micropipettes made of Tb3+-doped glass allows for various operations on GFP-labeled cells under real-time fluorescence microscopic control.
Article
Chemistry, Multidisciplinary
Shuai Gao, Nieng Yan
Summary: This study reports the structures of Ca(v)1.1 bound with different drugs, revealing the molecular basis for their effects. The structures show that amlodipine and nifedipine have different impacts on Ca(v)1.1, while the two enantiomers of Bay K8644 as agonists are insufficient to maintain the activated state of the channel.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Pharmacology & Pharmacy
Tamara Timic Stamenic, Francesca M. Manzella, Stefan Maksimovic, Kathiresan Krishnan, Douglas F. Covey, Vesna Jevtovic-Todorovic, Slobodan M. Todorovic
Summary: This study further investigated the molecular mechanisms of neurosteroid-induced hypnosis. The results demonstrated the importance of the Ca(V)2.3 subtype of voltage-gated calcium channels in thalamocortical excitability and the oscillations that underlie neurosteroid-induced hypnosis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Marta Martini, Giorgio Rispoli
Summary: Some sensory disorders in hearing, vestibular, and vision can be attributed to voltage-gated Ca2+ channels in sensory cells. In this study, the Na+ current flowing through L- and R-type Ca2+ channels in labyrinth hair cells was investigated. The activation and deactivation of the Na+ current in L-type channels were affected by low Ca2+ concentration, resulting in increased current amplitude. The R-type Na+ current was partially blocked by nifedipine and its current amplitude increased in low Ca2+ condition. Furthermore, the selectivity filter of R channels was less affected by external Ca2+ compared to L channels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)