Review
Chemistry, Medicinal
James R. Groome
Summary: This article reviews the study of marine toxins, particularly on their actions on sodium ion channels regulated by transmembrane voltage and neurotransmitters. The focus is on the diverse conotoxin peptides and their potential applications in evolutionary relationships, biological actions, disease therapy, and understanding the structure of ion channels at the atomic level.
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
Biochemistry & Molecular Biology
Kirsten L. Mcmahon, Henrik O'Brien, Christina I. Schroeder, Jennifer R. Deuis, Dhananjeyan Venkatachalam, Di Huang, Brad R. Green, Pradip K. Bandyopadhyay, Qing Li, Mark Yandell, Helena Safavi-Hemami, Baldomero M. Olivera, Irina Vetter, Samuel D. Robinson
Summary: This study identified new mu-conotoxins from species of the subgenera Textilia and Afonsoconus and investigated their selectivity at human Na-V channels using RNA-seq and DNA analysis techniques.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Anesthesiology
Jane E. Hartung, Jamie K. Moy, Emanuel Loeza-Alcocer, Vidhya Nagarajan, Ruth Jostock, Thomas Christoph, Wolfgang Schroeder, Michael S. Gold
Summary: This study characterized the high voltage-activated calcium currents in human and rat sensory neurons, revealing differences between the two species. The results showed significant differences in current density, sensitivity, and inhibition between human and rat neurons.
Article
Pharmacology & Pharmacy
Ian H. H. Kimball, Phuong T. T. Nguyen, Baldomero M. M. Olivera, Jon T. T. Sack, Vladimir Yarov-Yarovoy
Summary: In this study, the interactions between mu-Conotoxin KIIIA and the human Na(V)1.7 channel were investigated using Rosetta computational modeling and in silico docking. The specific pairwise contacts between KIIIA and hNa(V)1.7 were predicted using RosettaDock and experimentally validated. Comparison with the cryo-EM structure of KIIIA-hNa(V)1.2 revealed important similarities and differences between Na-V channel subtypes, which may have implications for understanding the molecular mechanism of toxin block. The integrative approach used in this study suggests that Rosetta structural predictions can be useful for designing biologics targeting specific Na-V channels.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chiung-Wei Huang, Pi-Chen Lin, Jian-Lin Chen, Ming-Jen Lee
Summary: The study revealed that CBD selectively binds to the slow-inactivated state of the Na(v)1.4 channel with a higher affinity and faster binding kinetics compared to the fast inactivation state. This differential inhibition of sodium current by CBD suggests its potential therapeutic benefit in treating myotonia resulting from sodium channelopathy.
Article
Pharmacology & Pharmacy
Meng-ting Li, Ya-ya Du, Fei Zhong, Jie-ru Wang, You-wei Gu, Yue Zhang, Xuan-tong Huang, Yi-zhou Deng, Zheng-xin Xu
Summary: Aloperine (ALO), a quinolizidine alkaloid from Sophora alopecuroides L., has anti-arrhythmic effects on ventricular arrhythmia, partially attributed to the inhibition of peak sodium current density of voltage-gated Na+ channel currents (I-Na).
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Neurosciences
Daniel M. DuBreuil, Eduardo Javier Lopez Soto, Simon Daste, Remy Meir, Daniel Li, Brian Wainger, Alexander Fleischmann, Diane Lipscombe
Summary: Functional Ca(V)2.2 channels in peripheral axons innervating skin are required for capsaicin-induced heat hypersensitivity, which may be an important therapeutic target for certain forms of chronic pain.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Yangmei Li, Chao Chang, Zhi Zhu, Lan Sun, Chunhai Fan
Summary: The dysfunction of voltage-gated calcium channels leading to a deficiency in Ca2+ fluxes is associated with calcium channelopathies such as epilepsy and periodic paralysis. By using resonant terahertz waves, researchers have demonstrated enhanced selectivity and conductance of Ca2+, potentially offering therapeutic interventions in correcting calcium channel deficiencies and inducing apoptosis in tumor cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Biochemistry & Molecular Biology
Xin Wu, Liang Hong
Summary: Calmodulin (CaM) is a small protein that serves as a ubiquitous signal transducer, regulating neuronal plasticity, muscle contraction, and immune response. It interacts with ion channels and plays regulatory roles in cellular electrophysiology. Mutations in CaM-binding IQ domain can lead to various diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Yichen Liu, Carlos A. Z. Bassetto, Bernardo I. Pinto, Francisco Bezanilla
Summary: In this study, authors have reinterpreted the mechanism of fast inactivation in eukaryotic Na+ channels based on structural analysis and current measurements. They found that the final inactivation gate in Nav1.4 channel is comprised of two hydrophobic rings that close downstream of IFM binding. This alternative molecular framework provides a new understanding of fast inactivation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Altin Sula, David Hollingworth, Leo C. T. Ng, Megan Larmore, Paul G. DeCaen, B. A. Wallace
Summary: This study identified a previously unidentified receptor site within the NavMs voltage-gated sodium channel, where tamoxifen and its metabolic products bind, inhibiting sodium conductance and potentially leading to the development of new drugs for sodium channelopathies.
Article
Multidisciplinary Sciences
Shuo Han, Xiang-Ping Chu, Ryan Goodson, Prae Gamel, Sophia Peng, Joshua Vance, Shizhen Wang
Summary: Cholesterol inhibits the hHv1 channel by stabilizing the voltage-sensing S4 segment at resting conformations, providing a mechanism for the regulation of fertilization by the hHv1 channel.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Jinqin Chen, Xinhong Liu, Shuo Yu, Jia Liu, Rongfang Chen, Yunxiao Zhang, Ling Jiang, Qiuyun Dai
Summary: Bu8 is a novel omega-conotoxin that is more potent than MVIIA, showing strong analgesic effects in animal pain models with fewer side effects. Its faster binding rate and higher recovery ratios contribute to its lower side effects, and its structure-activity relationships provide new insights for designing CaV2.2 antagonists.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Food Science & Technology
Kirsten L. McMahon, Hue N. T. Tran, Jennifer R. Deuis, David J. Craik, Irina Vetter, Christina Schroeder
Summary: mu-Conotoxins are peptide inhibitors of Na(V)1.7 channel with potential analgesic effects. Different mu-Conotoxins show varying selectivity towards hNa(V)1.7, with variations in loop 3 residue number and charged residues in this region affecting the selectivity. Additionally, the loop 1 extension in SxIIIC improves the inhibitory potency at hNa(V)1.7 compared to KIIIA.