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)
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
Paz Duran, Santiago Loya-Lopez, Dongzhi Ran, Cheng Tang, Aida Calderon-Rivera, Kimberly Gomez, Harrison J. Stratton, Sun Huang, Ya-ming Xu, E. M. Kithsiri Wijeratne, Samantha Perez-Miller, Zhiming Shan, Song Cai, Anna T. Gabrielsen, Angie Dorame, Kyleigh A. Masterson, Omar Alsbiei, Cynthia L. Madura, Guoqin Luo, Aubin Moutal, John Streicher, Gerald W. Zamponi, A. A. Leslie Gunatilaka, Rajesh Khanna
Summary: This study identified argentatin C, a compound derived from the Native American medicinal plant Parthenium incanum, which can block the activity of voltage-gated sodium and calcium channels and has potential as a novel treatment for painful conditions. Experimental results demonstrated that argentatin C decreased ion currents and excitability in sensory neurons and relieved postsurgical pain in a mouse model. Therefore, argentatin C may serve as an alternative therapy for chronic pain management.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Daohua Jiang, Jiangtao Zhang, Zhanyi Xia
Summary: Voltage-gated sodium channels are crucial for the rapid rising-phase of action potentials, and their mutations can lead to various human diseases. Recent studies using cryo-EM structures have provided valuable insights into the mechanism of eukaryotic Na-V channels, offering templates for drug development.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Shana L. Geffeney, Jennie Ann Cordingley, Kenyon Mitchell, Charles T. Hanifin
Summary: Multiple animal species have developed resistance to the neurotoxin tetrodotoxin (TTX) by altering the amino acid substitutions in voltage-gated sodium ion channels (VGSCs). This study demonstrates that positionally convergent substitutions of amino acids do not generate similar patterns among TTX-resistant animal lineages, suggesting that flexibility and movement of the protein may play a greater role in causing changes in TTX block.
Article
Pathology
Yuan Bian, Jiale Tuo, Liangpeng He, Wenwen Li, Shangxiao Li, Huiying Chu, Yongshan Zhao
Summary: Abnormal expression of VGSCs has been observed in tumors, and blocking VGSCs may present a new strategy for cancer treatment.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Review
Endocrinology & Metabolism
Nihal Ozturk, Serkan Uslu, Semir Ozdemir
Summary: Diabetes affects the heart through various mechanisms, including microvascular defects, metabolic abnormalities, and electrophysiological changes, leading to diabetic cardiomyopathy (DCM) which can cause structural and functional changes in the heart. DCM progresses to cause electrical remodeling, left ventricular dysfunction, and heart failure, contributing significantly to arrhythmias and sudden cardiac death in diabetes patients.
WORLD JOURNAL OF DIABETES
(2021)
Review
Pharmacology & Pharmacy
Tamer M. Gamal El-Din, Michael J. Lenaeus
Summary: Voltage-gated sodium channels are crucial proteins involved in action potential initiation and propagation. Recent studies have shown that fenestrations in these channels play important roles in drug binding and gating processes. Understanding the mechanisms of these channels and their associated diseases has significant implications for developing targeted therapeutics.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
Elisabetta Tosti, Raffaele Boni, Alessandra Gallo
Summary: Voltage-gated ion channels are membrane proteins that generate electrical signals, and their dysfunction can lead to diseases and pain. Conotoxins, bioactive peptides extracted from marine mollusk venom, have therapeutic effects and can relieve pain, but they may also cause pathological states.
Review
Neurosciences
George Goodwin, Stephen B. McMahon
Summary: Evidence from human genetic pain disorders shows that voltage-gated sodium channel alpha-subtypes Nav1.7, Nav1.8 and Nav1.9 play important roles in peripheral pain signaling. Drug development targeting these channels requires a better understanding of their involvement in pain signal transmission.
NATURE REVIEWS NEUROSCIENCE
(2021)
Article
Cell Biology
Samantha Edenfield, Abigail M. Sims, Constance Porretta, Harry J. Gould, Dennis Paul
Summary: This study demonstrated that the expression of VGSCs doubles during the preparation phase of cell division, while the expression of Na+,K+-ATPase only increases by 1.5 times. This finding has important implications for understanding the role of sodium in cell cycle control and the variability of treatments targeting these components of the Na+ handling system.
Article
Pharmacology & Pharmacy
Christopher Katnik, Javier Cuevas
Summary: The study focuses on intracellular ionic imbalance resulting from ischemic stroke, and the impact of NKCC1 antagonists on Na+ and Ca2+ overload. Loop diuretics BMN and EA inhibited ischemia-acidosis induced Ca2+ overload, but did not reduce Na+ increases.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Rahul Kumar Rathour, Hanoch Kaphzan
Summary: This study investigates the impact of variability in voltage-gated ion channels (VGICs) expression on information transfer. The results show that the expression variability of VGICs leads to variability in mutual information transfer and affects output firing frequencies. Virtual knockout experiments demonstrate that the A-type K+ channel plays a major role in information processing and transfer.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Jiangtao Zhang, Yiqiang Shi, Junping Fan, Huiwen Chen, Zhanyi Xia, Bo Huang, Juquan Jiang, Jianke Gong, Zhuo Huang, Daohua Jiang
Summary: This study reveals a novel mechanism for fast inactivation of voltage-gated sodium channels in Emiliania huxleyi, which is independent of the conventional Ile-Phe-Met motif. A N-terminal helix of Na(V)Eh blocks the activation gate to achieve fast inactivation. This mechanism enables rapid inactivation but delayed recovery compared to human Na-V channels.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Lei Zhang, Chenyang Zhang, Xin Dong, Zeyuan Dong
Summary: In this study, artificial supramolecular lithium channels composed of pore-containing small aromatic molecules were developed for the treatment of psychiatric disorders. These channels showed unprecedented transmembrane transport of exogenous lithium ions with high selectivity. The discovery of the basic requirements for ion transport function in these channels may have important implications in studying the physiological role of intracellular lithium ions and treating psychiatric disorders.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)