Article
Cardiac & Cardiovascular Systems
K. G. Kreitmeier, D. Tarnowski, M. S. Nanadikar, M. J. Baier, S. Wagner, D. M. Katschinski, L. S. Maier, C. M. Sag
Summary: The study demonstrates that the activation of CaMKII delta through Met281/282 oxidation is not necessary for the recovery of Ca2+ transients during acidosis or for the occurrence of postacidic cellular arrhythmias. Despite an usually prooxidant increase in cytosolic Na+, acidosis reduces the cytosolic glutathione redox state within cardiac myocytes, suggesting that oxidation of cytosolic proteins is less likely to occur during acidosis.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Lei Yang, Rong-Chang Li, Bin Xiang, Yi-Chen Li, Li-Peng Wang, Yun-Bo Guo, Jing-Hui Liang, Xiao-Ting Wang, Tingting Hou, Xin Xing, Zeng-Quan Zhou, Haihong Ye, Ren-Qing Feng, Edward G. Lakatta, Zhen Chai, Shi-Qiang Wang
Summary: The contraction of heart cells is regulated by the signaling interaction between LCCs and RyRs, which is influenced by the nanodistance between JPH2 in the SR and CAV3 in the TT. Our study revealed that SRF and myocardin concurrently regulate the expression of JPH2 and CAV3, leading to enhanced efficiency of LCC-RyR signaling and compensation for LCC down-regulation during hibernation, maintaining heart power and avoiding calcium overload.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Xueyong Wang, Murad Nawaz, Chris DuPont, Jessica H. Myers, Steve Ra Burke, Roger A. Bannister, Brent D. Foy, Andrew A. Voss, Mark M. Rich
Summary: Excitation-contraction coupling is the process of converting electrical excitation of muscle into force generation. Depolarization of skeletal muscle can lead to failure of ECC, specifically the failure to generate calcium transients. Different AP properties, such as AP peak and AP integral, play important roles in different steps of ECC, including AP conduction and calcium release.
Review
Toxicology
Joshua A. Keefe, Oliver M. Moore, Kevin S. Ho, Xander H. T. Wehrens
Summary: This review provides a comprehensive overview of the roles of Ca2+-handling proteins in healthy cardiac function and the mechanisms by which mutations in these proteins contribute to inherited arrhythmias. The major Ca2+ channels and Ca2+-sensitive regulatory proteins involved in cardiac excitation-contraction coupling are discussed, with special emphasis on the function of the RyR2 macromolecular complex. Inherited arrhythmia disorders caused by mutations in Ca2+-handling proteins are also discussed.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Neurosciences
Daiki Watanabe, Ryo Ikegami, Yutaka Kano
Summary: This study investigated the mechanisms underlying faster force recovery from eccentric contractions in female mice compared to male mice. Superior mitochondrial responses and the contribution of estrogen were found to play a significant role in the faster recovery of force in females. These findings highlight the importance of mitochondrial function and estrogen in sex differences in force recovery.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Multidisciplinary Sciences
Zheng Fang Yang, Pankaj Panwar, Ciaran R. McFarlane, Wietske E. Tuinte, Marta Campiglio, Filip Van Petegem
Summary: Junctophilins (JPH) are proteins that connect the plasma membrane and the endoplasmic or sarcoplasmic reticulum, facilitating communication between proteins in different membranes. This study presents crystal structures of two JPH isoforms, revealing their importance in muscle excitation-contraction coupling. Various mutations in JPH2 and the L-type calcium channel affect their interaction and have been linked to cardiomyopathy and cardiac arrhythmia, respectively.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Zhilin Qu, Dasen Yan, Zhen Song
Summary: This article reviews the progress and challenges in modeling intracellular calcium cycling in the cardiac system. The calcium release channels in cardiac myocytes form a network that gives rise to various dynamic processes. Modeling the intracellular calcium cycling dynamics in the cardiac system is challenging due to its complexity.
Article
Cardiac & Cardiovascular Systems
Deborah Peana, Luis Polo-Parada, Timothy L. Domeier
Summary: TRPV4 contributes to pro-arrhythmic cardiomyocyte Ca2+ signalling, electrophysiological abnormalities, and ventricular arrhythmia in the aged mouse heart.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cell Biology
Jaime Balderas-Villalobos, J. M. L. Medina-Contreras, Christopher Lynch, Rajiv Kabadi, Rafael J. Ramirez, Alex Y. Tan, Karoly Kaszala, Montserrat Samso, Jose F. Huizar, Jose M. Eltit
Summary: Premature ventricular contractions (PVCs) are common ventricular arrhythmias that can enhance contractility acutely but lead to cardiomyopathy over time. Altered Ca2+ reuptake, as observed in PVC-CM, may contribute to contractile dysfunction. Study findings suggest delayed Ca2+ reuptake, reduced SERCA2 activity, and altered expression and phosphorylation of SERCA2 and PLB in PVC-CM. These alterations moderately contribute to functional adaptations in PVC-CM.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Cardiac & Cardiovascular Systems
Cherrie H. T. Kong, Mark B. Cannell
Summary: Cardiac excitation-contraction coupling relies on Ca2+ release from intracellular stores triggered by L-type Ca2+ channels. Our study found that voltage changes and channel gating stochasticity can lead to variability in Ca2+ spark timing, but the Ca2+ transient wavefronts remain remarkably consistent. Experimental and computational modeling showed that there may be 4 Ca2+ spark initiating complexes per couplon, which decreases spark latency and increases spark probability.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Article
Multidisciplinary Sciences
Chien-Wen S. Kuo, Sara Dobi, Caglar Goek, Ana Da Silva Costa, Alice Main, Olivia Robertson-Gray, Daniel Baptista-Hon, Krzysztof J. Wypijewski, Hannah Costello, Tim G. Hales, Niall MacQuaide, Godfrey L. Smith, William Fuller
Summary: The α1C subunit of L-type Ca2+ channels, responsible for transmembrane Ca2+ fluxes, undergoes reversible palmitoylation in rat, rabbit, and human ventricular myocytes. The sites of palmitoylation are found in the N terminus and the linker between domains I and II of the channel. Unpalmitoylated α1C subunit leads to reduced voltage sensitivity of Ca2+ channels.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cardiac & Cardiovascular Systems
Masahito Miura, Taiki Hasegawa, Ayana Matsumoto, Masami Nishiyama, Yuka Someya, Wakako Satoh, Kazunori Kumasaka, Chiyohiko Shindoh, Haruka Sato
Summary: This study suggests that transient elevation of blood glucose for 1 hour in non-diabetic hearts under higher Ca2+-load reduces contractile properties probably by activating CaMKII through O-GlcNAcylation. Therefore, in patients with severe disease, such as acute myocardial infarction or acute heart failure, transient elevation of blood glucose could worsen cardiac function and affect mortality without known diabetes.
Article
Biochemistry & Molecular Biology
Yu-Wang Chang, Yong-Cyuan Chen, Chien-Chang Chen
Summary: The Cav3.2 T-type calcium channel plays a crucial role in various pathological conditions, and its calcium channel function is regulated by phosphorylation by multiple kinases. In this study, we used quantitative mass spectrometry to identify the serine/threonine residues on Cav3.2 that are dephosphorylated by calcineurin. We found six dephosphorylated serine residues in different regions of Cav3.2, and observed that calcineurin binds to and dephosphorylates the C-terminus of Cav3.2. Additionally, we discovered that calcineurin can dephosphorylate a previously known CaMKII-phosphorylated site (S1198) and a novel CaMKII-phosphorylated site (S2137) on Cav3.2. These findings provide insights into the regulation of Cav3.2 through both kinase phosphorylation and calcineurin phosphatase dephosphorylation.
Article
Neurosciences
Martin Laasmaa, Jelena Branovets, Jekaterina Stolova, Xin Shen, Triinu Ratsepso, Mihkel Jaan Balodis, Caerolin Grahv, Eliise Hendrikson, William Edward Louch, Rikke Birkedal, Marko Vendelin
Summary: There are sex differences in the structural organization of transverse tubular network and ryanodine receptors in the heart, as well as in the response to adrenergic stimulation with isoprenaline.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Cardiac & Cardiovascular Systems
Monika Seidel, Camille Rabesahala de Meritens, Louisa Johnson, Dimitris Parthimos, Mark Bannister, Nia Lowri Thomas, Esizaze Ozekhome-Mike, Francis Anthony Lai, Spyros Zissimopoulos
Summary: The study characterizes the network of interactions regulating the activity of the RyR2 homotetramer, identifying the importance of a peptide sequence bridging the beta 8 with beta 9 strand in mediating N-terminus self-association. The beta 8-beta 9 loop is crucial for N-terminal intersubunit interaction, while also interacting with the C-terminal channel pore region in a Ca2+-independent manner. Deletion of the beta 8-beta 9 sequence affects RyR2 subunit oligomerization and intracellular Ca2+ mobilization, indicating a role in channel opening.
CARDIOVASCULAR RESEARCH
(2021)
Review
Cell Biology
Glynnis A. Garry, Rhonda Bassel-Duby, Eric N. Olson
Summary: Ischemic heart disease is the leading cause of morbidity and mortality worldwide, and finding new ways to promote cardiomyocyte regeneration is crucial. Direct reprogramming of cardiac fibroblasts into induced cardiac-like myocytes (iCMs) has shown promising potential, but there are challenges in reprogramming adult human fibroblasts.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Catherine A. Makarewich, Amir Z. Munir, Svetlana Bezprozvannaya, Aaron M. Gibson, Soo Young Kim, Misty S. Martin-Sandoval, Thomas P. Mathews, Luke I. Szweda, Rhonda Bassel-Duby, Eric N. Olson
Summary: New evidence suggests that certain noncoding RNA molecules actually code for microproteins. By using comparative genomics, researchers identified a microprotein called Mtlbn that is abundantly expressed in the heart. Mtlbn localizes to the inner mitochondrial membrane and interacts with subunits of the electron transport chain and respiratory supercomplexes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Peiheng Gan, Zhaoning Wang, Maria Gabriela Morales, Yu Zhang, Rhonda Bassel-Duby, Ning Liu, Eric N. Olson
Summary: This study identified a genetic defect associated with noncompaction cardiomyopathy and revealed some underlying mechanisms. The loss of Rbpms gene led to premature cardiomyocyte binucleation and cell cycle arrest, in which Rbpms mediated the isoform switching of a specific protein.
DEVELOPMENTAL CELL
(2022)
Article
Medicine, Research & Experimental
Dileep R. Karri, Yu Zhang, Francesco Chemello, Yi-Li Min, Jian Huang, Jiwoong Kim, Pradeep P. A. Mammen, Lin Xu, Ning Liu, Rhonda Bassel-Duby, Eric N. Olson
Summary: This study demonstrates the long-term durability of CRISPR/Cas9 genome editing as a therapy for maintaining the integrity and function of DMD muscle, even under conditions of stress.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Cardiac & Cardiovascular Systems
Ning Liu, Eric N. Olson
Summary: Cardiovascular disease is the leading cause of deaths and illnesses in developed countries. Mouse models have played a significant role in studying the complex signaling pathways, genetic and epigenetic regulations, and multicellular interactions involved in cardiovascular disease. The advent of CRISPR genome editing has revolutionized cardiovascular research, allowing for rapid modeling and potential genetic correction of disease-causing mutations.
CIRCULATION RESEARCH
(2022)
Article
Geriatrics & Gerontology
Mina Shahriyari, Md Rezaul Islam, Sadman M. Sakib, Malte Rinn, Anastasia Rika, Dennis Krueger, Lalit Kaurani, Verena Gisa, Mandy Winterhoff, Harithaa Anandakumar, Orr Shomroni, Matthias Schmidt, Gabriela Salinas, Andreas Unger, Wolfgang A. Linke, Jana Zschuentzsch, Jens Schmidt, Rhonda Bassel-Duby, Eric N. Olson, Andre Fischer, Wolfram-Hubertus Zimmermann, Malte Tiburcy
Summary: This study successfully established methods for deriving skeletal muscle cells from human pluripotent stem cells and engineered a functional human skeletal muscle organoid and engineered skeletal muscle with regeneration-competent satellite-like cells. Contractile performance of the engineered muscle was further enhanced by thyroid hormone treatment.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Medicine, Research & Experimental
Yu Zhang, Hui Li, Takahiko Nishiyama, John R. McAnally, Efrain Sanchez-Ortiz, Jian Huang, Pradeep P. A. Mammen, Rhonda Bassel-Duby, Eric N. Olson
Summary: In this study, a humanized DMD mouse model was created to evaluate the efficacy of CRISPR-Cas9 gene editing for DMD correction. The model successfully restored dystrophin expression and improved pathological features and muscle strength. This model provides a valuable tool for assessing clinically relevant gene editing strategies and advancing the therapeutic translation of CRISPR-Cas9 gene editing for DMD correction.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Immunology
Ildiko Bock-Marquette, Klaudia Maar, Szabolcs Maar, Balint Lippai, Gabor Faskerti, Ferenc Gallyas, Eric N. Olson, Deepak Srivastava
Summary: Our dream of defeating the processes of organ damage and aging remains a challenge, and steps towards regenerating individual organs are considered significant. Through interconnecting our collective knowledge regarding aging and embryonic development, we propose to discover molecules that can effectively reverse cellular damage. Our results regarding Thymosin beta-4 (TB4) support this hypothesis, showing its potential to promote cardiac cell migration and survival, enhance myocyte survival and improve cardiac function, and activate epicardial progenitor cells.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Xurde M. Caravia, Andres Ramirez-Martinez, Peiheng Gan, John R. McAnally, Rhonda Bassel-Duby, Ning Liu, Eric N. Olson
CIRCULATION RESEARCH
(2022)
Article
Medicine, Research & Experimental
Xurde M. Caravia, Andres Ramirez-Martinez, Peiheng Gan, Feng Wang, John R. McAnally, Lin Xu, Rhonda Bassel-Duby, Ning Liu, Eric N. Olson
Summary: Mutations in nuclear envelope proteins cause devastating genetic diseases that primarily affect the heart and skeletal muscle. This study reveals the essentiality of LEMD2 for genome stability and cardiac function, and uncovers its mechanistic association with human disease. Gene therapy targeting Lemd2 can rescue the disease phenotype.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Miao Cui, Ning Liu, Rhonda S. Bassel-Duby, Eric N. Olson
CIRCULATION RESEARCH
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
I. Bock-Marquette, K. Maar, S. Maar, B. Lippai, G. Faskerti, D. Hanna, J. Thatcher, E. N. Olson, F. Gallyas
EUROPEAN JOURNAL OF HEART FAILURE
(2022)
Meeting Abstract
Transplantation
Tobias Bohnenpoll, Eric Olson, Mykola Dergai, Jennifer Cox, Simone Romoli, I-Ju Lo, Johannes Pospiech, Krishan Vishnolia, Mark Mcconnell, Marvin Gunawan, Michaela Bayerlova, Nicolette Honson, Niklas Michel, Nikolas Stroth, Olivier Radresa, Philipp Skroblin, Priyanka Kohli, Seamus Ragan, Shenshen Lai, Steven Bromidge, David Powell, Uwe Andag, Andrew King
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
Meeting Abstract
Transplantation
Eric Olson, Mark Mcconnell, Seamus Ragan, Jennifer Cox, Jeff Lester, Charles Nieh, Jay Kuo, Andrew King
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
Article
Medicine, Research & Experimental
Andres Ramirez-Martinez, Yichi Zhang, Marie-Jose Van den Boogaard, John R. McAnally, Cristina Rodriguez-Caycedo, Andreas C. Chai, Francesco Chemello, Maarten P. G. Massink, Inge Cuppen, Martin G. Elferink, Robert J. J. van Es, Nard G. Janssen, Linda P. A. M. Walraven-van Oijen, Ning Liu, Rhonda Bassel-Duby, Richard H. van Jaarsveld, Eric N. Olson
Summary: The study identifies a variant of the MYMX gene that is associated with CFZS-like abnormalities, leading to impaired fusion activity. Patient-derived cells and mouse models confirm the pathogenic role of this variant and CRISPR/Cas9 gene editing shows potential for therapeutic intervention.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
