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
Diane C. A. Barret, Dina Schuster, Matthew J. Rodrigues, Alexander Leitner, Paola Picotti, Gebhard F. X. Schertler, U. Benjamin Kaupp, Volodymyr M. Korkhov, Jacopo Marino
Summary: Calmodulin (CaM) regulates ion channels to control calcium entry into cells, and mutations affecting this interaction are linked to fatal diseases. The structural basis of CaM regulation is not well understood. In retinal photoreceptors, CaM binds to the CNGB subunit of CNG channels and modulates the channel's sensitivity to changes in ambient light. This study provides the structural characterization of CaM regulation of a CNG channel using cryo-electron microscopy and proteomics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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.
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
Cell Biology
Adam Feher, Marianna Pocsi, Ferenc Papp, Tibor G. Szanto, Agota Csoti, Zsolt Fejes, Bela Nagy, Balazs Nemes, Zoltan Varga
Summary: This study identified multiple voltage-gated sodium channels in the plasma membrane of human B cells using electrophysiological and molecular biology methods. The detected sodium currents showed sensitivity between TTX-sensitive and TTX-insensitive channels, suggesting the co-existence of multiple Na(V)1 subtypes. The results also supported the functional role of these channels in shaping and maintaining the resting membrane potential.
Article
Pharmacology & Pharmacy
Lihua Chen, Lena Al-Harthi, Xiu-Ti Hu
Summary: Combination antiretroviral therapy (cART) can suppress HIV-1 replication, improve immune function, but also induce neurotoxicity. Triumeq, a common cART regimen, was found to affect pyramidal neurons in the rat brain cortex in relation to Ca2+ channels.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Physiology
Jamie S. S. Lindner, Salil R. R. Rajayer, Briana J. J. Martiszus, Stephen M. M. Smith
Summary: The calcium-sensing receptor agonist, cinacalcet, regulates neuronal excitability by modulating the voltage-dependence of voltage-gated sodium channel (VGSC) currents. This regulation is achieved by shifting the voltage-dependence of VGSC currents and involves an unidentified inhibitory molecule that is G-protein dependent.
FRONTIERS IN PHYSIOLOGY
(2022)
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
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
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
Sigrid Noreng, Tianbo Li, Jian Payandeh
Summary: Voltage-gated sodium channels play crucial roles in physiological processes, and recent breakthroughs in cryo-electron microscopy have advanced our understanding of their structure and pharmacological action. This provides new insights for the design of drugs targeting Na channels.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
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
Cell Biology
Daniel Gratz, Alexander J. Winkle, Seth H. Weinberg, Thomas J. Hund
Summary: Bayesian statistics methods were used to capture variability in experimental measurements of human atrial Na(v)1.5, leading to the establishment of a novel model that incorporated physiological distribution of model parameters. Model validation was conducted by comparing simulated and experimental measurements of action potential upstroke velocity, with plans to extend the approach to other atrial ion channels for a comprehensive model of human atrial action potential.
Article
Biochemistry & Molecular Biology
Julien Giribaldi, Jean Chemin, Marie Tuifua, Jennifer R. Deuis, Rosanna Mary, Irina Vetter, David T. Wilson, Norelle L. Daly, Christina I. Schroeder, Emmanuel Bourinet, Sebastien Dutertre
Summary: A novel spider toxin, named Pmu1a, was discovered from the venom of Pterinochilus murinus. It has inhibitory activity on both hNa(V)1.7 and hCa(V)3.2 channels, which are therapeutic targets involved in pain pathways. This finding may lead to the development of compounds targeting these channels for chronic pain treatment.
Article
Chemistry, Physical
Mehdi Yoosefian, Batool Tajaddini, Saeid Ahmadzadeh, Maryam Zeraati-Moghani, Zahra Pakdin-Parizi
Summary: Drinking excessive alcohol can cause chronic diseases and serious problems such as heart disease, high blood pressure, stroke, digestive problems, and liver disease. A molecular dynamics simulation study found that ethanol blocks calcium channels and interferes with calcium ion passage. Furthermore, calcium ions have a greater tendency to interact with residues inside the protein channel in the presence of ethanol.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Cardiac & Cardiovascular Systems
Nieves Gomez-Hurtado, Nicole J. Boczek, Dmytro O. Kryshtal, Christopher N. Johnson, Jennifer Sun, Florentin R. Nitu, Razvan L. Cornea, Walter J. Chazin, Melissa L. Calvert, David J. Tester, Michael J. Ackerman, Bjorn C. Knollmann
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
(2016)
Article
Cardiac & Cardiovascular Systems
Nicole J. Boczek, Nieves Gomez-Hurtado, Dan Ye, Melissa L. Calvert, David J. Tester, Dmytro O. Kryshtal, Hyun Seok Hwang, Christopher N. Johnson, Walter J. Chazin, Christina G. Loporcaro, Maully Shah, Andrew L. Papez, Yung R. Lau, Ronald Kanter, Bjoern C. Knollmann, Michael J. Ackerman
CIRCULATION-CARDIOVASCULAR GENETICS
(2016)
Letter
Cardiac & Cardiovascular Systems
Kafa Walweel, Nieves Gomez-Hurtado, Ye Wint Oo, Nicole A. Beard, Cris dos Remedios, Christopher N. Johnson, Walter J. Chazin, Walter J. Chazin, Dirk F. van Helden, Bjorn C. Knollmann, Derek R. Laver
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Christopher N. Johnson, Franck Potet, Matthew K. Thompson, Brett M. Kroncke, Andrew M. Glazer, Markus W. Voehler, Bjorn C. Knollmann, Alfred L. George, Walter J. Chazin
Review
Physiology
Przemyslaw B. Radwanski, Christopher N. Johnson, Sandor Gyorke, Rengasayee Veeraraghavan
FRONTIERS IN PHYSIOLOGY
(2018)
Article
Cell Biology
Christopher N. Johnson, Rekha Pattanayek, Franck Potet, Robyn T. Rebbeck, Daniel J. Blackwell, Roman Nikolaienko, Vasco Sequeira, Remy Le Meur, Przemyslaw B. Radwanski, Jonathan P. Davis, Aleksey Zima, Razvan L. Cornea, Steven M. Damo, Sandor Gyorke, Alfred L. George, Bjorn C. Knollmann
Article
Cardiac & Cardiovascular Systems
Lisa M. Wren, Juan Jimenez-Jaimez, Saleh Al-Ghamdi, Jumana Y. Al-Aama, Amnah Bdeir, Zuhair N. Al-Hassnan, Jyn L. Kuan, Roger Y. Foo, Franck Potet, Christopher N. Johnson, Miriam C. Aziz, Gemma L. Carvill, Juan-Pablo Kaski, Lia Crotti, Francesca Perin, Lorenzo Monserrat, Paul W. Burridge, Peter J. Schwartz, Walter J. Chazin, Zahurul A. Bhuiyan, Alfred L. George
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2019)
Review
Biochemistry & Molecular Biology
Walter J. Chazin, Christopher N. Johnson
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Medicine, Research & Experimental
Josine M. de Winter, Joery P. Molenaar, Michaela Yuen, Robbert van der Pijl, Shengyi Shen, Stefan Conijn, Martijn van de Locht, Menne Willigenburg, Sylvia J. P. Bogaards, Esmee S. B. van Kleef, Saskia Lassche, Malin Persson, Dilson E. Rassier, Tamar E. Sztal, Avnika A. Ruparelia, Viola Oorschot, Georg Ramm, Thomas E. Hall, Zherui Xiong, Christopher N. Johnson, Frank Li, Balazs Kiss, Noelia Lozano-Vidal, Reinier A. Boon, Manuela Marabita, Leonardo Nogara, Bert Blaauw, Richard J. Rodenburg, Benno Kusters, Jonne Doorduin, Alan H. Beggs, Henk Granzier, Ken Campbell, Weikang Ma, Thomas Irving, Edoardo Malfatti, Norma B. Romero, Robert J. Bryson-Richardson, Baziel G. M. van Engelen, Nicol C. Voermans, Coen A. C. Ottenheijm
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Multidisciplinary Sciences
D. Julia Trembinski, Diewertje I. Bink, Kosta Theodorou, Janina Sommer, Ariane Fischer, Anke van Bergen, Chao-Chung Kuo, Ivan G. Costa, Christoph Schuermann, Matthias S. Leisegang, Ralf P. Brandes, Tijna Alekseeva, Boris Brill, Astrid Wietelmann, Christopher N. Johnson, Alexander Spring-Connell, Manuel Kaulich, Stanislas Werfel, Stefan Engelhardt, Marc N. Hirt, Kaja Yorgan, Thomas Eschenhagen, Luisa Kirchhof, Patrick Hofmann, Nicolas Jae, Ilka Wittig, Nazha Hamdani, Corinne Bischof, Jaya Krishnan, Riekelt H. Houtkooper, Stefanie Dimmeler, Reinier A. Boon
NATURE COMMUNICATIONS
(2020)
Review
Biochemistry & Molecular Biology
Ryan B. Williams, Christopher N. Johnson
Summary: Calcineurin, also known as protein phosphatase 2B, is a crucial serine threonine phosphatase involved in multiple signaling pathways. Despite extensive research on its role in cardiac disease, clarification is needed on its physiological function in healthy cardiomyocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Bin Sun, Xuan Fang, Christopher N. Johnson, Garrett Hauck, Yongjun Kou, Jonathan P. Davis, Peter M. Kekenes-Huskey
Summary: Plant-derived CaM variants sCaM-1 and sCaM-4 exhibit similar Ca2+ and canonical CaMBR binding properties as mammalian CaM (mCaM), but show weakened binding with a secondary region in CaN, suggesting a mechanism for differential regulation of CaN activity that involves interactions beyond traditional Ca2+ and CaMBR binding.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Editorial Material
Physiology
Robert Szulcek, Christopher N. Johnson, James Todd Pearson, Vasco Sequeira
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cell Biology
Ryan B. Williams, Md Nure Alam Afsar, Svetlana Tikunova, Yongjun Kou, Xuan Fang, Radha P. Somarathne, Rita F. Gyawu, Garrett M. Knotts, Taylor A. Agee, Sara A. Garcia, Luke D. Losordo, Nicholas C. Fitzkee, Peter M. Kekenes-Huskey, Jonathan P. Davis, Christopher N. Johnson
Summary: Calmodulin (CaM) is a calcium-sensing protein that regulates various processes in the body. Mutations in CaM can lead to life-threatening heart disease. This study investigates how disease-associated CaM mutations affect the activity of the phosphatase protein CaN and suggests a potential contribution of altered CaN function to calmodulinopathy.