Article
Multidisciplinary Sciences
Cedric R. Lamboley, Luke Pearce, Crystal Seng, Aldo Meizoso-Huesca, Daniel P. Singh, Barnaby P. Frankish, Vikas Kaura, Harriet P. Lo, Charles Ferguson, Paul D. Allen, Philip M. Hopkins, Robert G. Parton, Robyn M. Murphy, Chris van der Poel, Christopher J. Barclay, Bradley S. Launikonis
Summary: The study reveals that RyR1 Ca2+ leak causes redistribution of Ca2+ among different cellular structures by altering the Ca2+ permeability of different membranes, impacting muscle function. Individuals with gain-of-function RYR1 mutations may experience reduced force generation and increased susceptibility to MH.
Article
Cardiac & Cardiovascular Systems
Matthew J. Wleklinski, Dmytro O. Kryshtal, Kyungsoo Kim, Shan S. Parikh, Daniel J. Blackwell, Isabelle Marty, V. Ramesh Iyer, Bjorn C. Knollmann
Summary: CASQ2-K180R causes CPVT2 through impairing dynamic buffering of Ca within the SR, which is different from other CASQ2-related forms of CPVT2.
CIRCULATION RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Maren E. Arnold, Wolfgang R. Dostmann, Jody Martin, Michael J. Previs, Bradley Palmer, Martin LeWinter, Markus Meyer
Summary: This study introduces a novel biosensor that can visualize the interaction between SERCA2a and phospholamban (PLB). The biosensor combines SERCA2a, a circularly permutated green fluorescent protein, and PLB into one recombinant protein (SGP). Activation of proteinkinase A leads to phosphorylation of the PLB domain, resulting in a significant increase in fluorescence yield for real-time monitoring of SERCA2a and PLB interactions in cells.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Article
Physiology
Molly E. E. Streiff, Andrea C. C. Corbin, Azmi A. A. Ahmad, Chris Hunter, Frank B. B. Sachse
Summary: Transient receptor potential canonical 1 (TRPC1) channels play a critical role in the physiological regulation of cardiac function and have implications in the development of cardiac diseases. This study reveals that TRPC1 channels are involved in the mechanosensitive modulation of sarcoplasmic reticulum Ca2+ concentration, highlighting their significance in cardiac physiology and potential as therapeutic targets for cardiac diseases.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Physiology
Molly E. Streiff, Frank B. Sachse
Summary: The regulation of Ca2+ concentrations in cardiomyocytes is crucial for various physiological processes. Two types of Ca2+ currents, background Ca2+ entry and Ca2+ leak from the sarcoplasmic reticulum, play important roles in the modulation of Ca2+ transients and Ca2+ load. Our study provides quantitative insights into the individual contributions of these Ca2+ currents and supports the hypothesis that TRP channels are involved in cardiac contractility modulation.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cell Biology
Sou Inagaki, Yoshiaki Suzuki, Keisuke Kawasaki, Rubii Kondo, Yuji Imaizumi, Hisao Yamamura
Summary: In this study, the role of mitochondrial fusion protein 2 (Mfn2) in the coupling of sarcoplasmic reticulum (SR) and mitochondria in vascular smooth muscle cells (VSMCs) was examined. It was found that Mfn2 is responsible for tethering mitochondria to SR, which regulates calcium signaling, ATP production, and cell proliferation in VSMCs.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Giampaolo Morciano, Alessandro Rimessi, Simone Patergnani, Veronica A. M. Vitto, Alberto Danese, Asrat Kahsay, Laura Palumbo, Massimo Bonora, Mariusz R. Wieckowski, Carlotta Giorgi, Paolo Pinton
Summary: Intracellular calcium signaling is a universal language shared by various biological entities inside cells, regulating physiological functions like muscle contraction through calcium channels, pumps, and exchangers. Abnormal calcium homeostasis can lead to heart diseases, but can be corrected through chemical, peptide-based, and pharmacological modulators.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Rizwan Qaisar, Gavin Pharaoh, Shylesh Bhaskaran, Hongyang Xu, Rojina Ranjit, Jan Bian, Bumsoo Ahn, Constantin Georgescu, Jonathan D. Wren, Holly Van Remmen
Summary: The study showed that pharmacological activation of SERCA can mitigate sarcopenia phenotype in aging mice, reversing reductions in muscle mass and force generation, and preventing an increase in mitochondrial ROS production. These effects are mediated in part by enhanced cellular energetics through activation of PGC1-alpha, UCP1, HSF1, and APMK, as well as increased regenerative capacity by suppression of MEF2C and p38 MAPK signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Weihong He, Charlotte S. McCarroll, Katrin Nather, Kristopher Ford, Kenneth Mangion, Alexandra Riddell, Dylan O'Toole, Ali Zaeri, David Corcoran, David Carrick, Mathew M. Y. Lee, Margaret McEntegart, Andrew Davie, Richard Good, Mitchell M. Lindsay, Hany Eteiba, Paul Rocchiccioli, Stuart Watkins, Stuart Hood, Aadil Shaukat, Lisa McArthur, Elspeth B. Elliott, John McClure, Catherine Hawksby, Tamara Martin, Mark C. Petrie, Keith G. Oldroyd, Godfrey L. Smith, Keith M. Channon, Colin Berry, Stuart A. Nicklin, Christopher M. Loughrey
Summary: The study identified that direct cardiac release of cathepsin-L in STEMI patients post-PPCI leads to elevated serum levels, and higher levels in the first 24 hours post-reperfusion are associated with reduced cardiac function and increased infarct size. Preclinical studies showed that inhibiting cathepsin-L release post-reperfusion injury can reduce infarct size and improve cardiac function by limiting abnormal calcium handling and apoptosis.
CARDIOVASCULAR RESEARCH
(2022)
Article
Neurosciences
David C. Hutchings, George W. P. Madders, Barbara C. Niort, Elizabeth F. Bode, Caitlin A. Waddell, Lori S. Woods, Katharine M. Dibb, David A. Eisner, Andrew W. Trafford
Summary: Ventricular arrhythmias can cause death in heart failure. This study investigates the mechanism by which raising external Ca2+ induces Ca2+ waves and how it is modified in heart failure. The results reveal a novel sarcolemmal background Ca2+ influx via the TRPC6 channel responsible for Ca2+ waves, and the increased propensity for Ca2+ waves in heart failure is due to increased background influx and decreased threshold SR content.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Review
Cardiac & Cardiovascular Systems
Shanna Hamilton, Radmila Terentyeva, Richard T. Clements, Andriy E. Belevych, Dmitry Terentyev
Summary: This article reviews the major cause of sudden cardiac death due to ventricular tachyarrhythmias and the enhanced propensity to malignant cardiac arrhythmias associated with heart failure, diabetic cardiomyopathy, old age related cardiac dysfunction and inherited disorders. Defective mitochondrial function and abnormal intracellular Ca2+ homeostasis have been established as key contributing factors to pathophysiology and arrhythmogenesis in these conditions. The article also discusses the bidirectional control of ryanodine receptor-mediated sarcoplasmic reticulum Ca2+ release and mitochondrial function, and how defects in crosstalk between these organelles increase arrhythmic risk in cardiac disease.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Yuxin Du, Laurie J. Demillard, Jun Ren
Summary: This article summarizes the normal regulation of SR Ca2+ in cardiomyocytes, the mechanisms of how Ca2+ triggers arrhythmias, the involvement of SR gene mutations in inherited arrhythmias, and the possible arrhythmogenic effects of these mutations.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Biology
Derek A. Terrar
Summary: Rhythms of electrical activity in the heart can be influenced by various intracellular organelles, including the sarcoplasmic reticulum, lysosomes, and mitochondria. These organelles can provide timing mechanisms and participate in signaling processes to affect cardiac electrical activity. Calcium ions play multiple roles in carrying electric current, driving sodium-calcium exchange, and activating enzymes. The interaction between intracellular organelles has profound effects on heart rhythms, with sodium-calcium exchange playing a central role.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Neurosciences
Daisuke Sato, Hitoshi Uchinoumi, Donald M. Bers
Summary: Increasing SERCA activity has a dual effect on the propensity of arrhythmogenic Ca waves, promoting their generation at lower levels but potentially aborting them at higher levels. Factors influencing Ca wave propagation include diffusive coupling between Ca sparks, Ca buffers, intra-SR Ca diffusion, and distance between CRUs.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Review
Physiology
Hiroaki Eshima
Summary: Obesity and diabetes can disrupt peripheral insulin resistance in skeletal muscle and lead to loss of muscle size, strength, and physical function, with contractile dysfunction being linked to impaired intracellular Ca2+ concentration regulation. Recent studies have shown that metabolic disorders affect interactions between the SR and mitochondrial networks, altering Ca2+ handling by these organelles. This review highlights the importance of understanding the impact of metabolic disorders on calcium regulation in skeletal muscle for potential therapeutic strategies.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Physiology
Siu-Lung Chan, Mark T. Nelson, Marilyn J. Cipolla
Article
Neurosciences
Nathan R. Tykocki, Thomas J. Heppner, Thomas Dalsgaard, Adrian D. Bonev, Mark T. Nelson
JOURNAL OF PHYSIOLOGY-LONDON
(2019)
Article
Cardiac & Cardiovascular Systems
Daniel M. Collier, Nuria Villalba, Adrian Sackheim, Adrian D. Bonev, Zachary D. Miller, Jesse S. Moore, Bo Shui, Jane C. Lee, Frank K. Lee, Shaun Reining, Michael Kotlikoff, Mark T. Nelson, Kalev Freeman
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2019)
Article
Cardiac & Cardiovascular Systems
Mario Kassmann, Istvan Andras Szijarto, Concha F. Garcia-Prieto, Gang Fan, Johanna Schleifenbaum, Yoland-Marie Anistan, Christoph Tabeling, Yu Shi, Ferdinand le Noble, Martin Witzenrath, Yu Huang, Lajos Marko, Mark T. Nelson, Maik Gollasch
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2019)
Article
Critical Care Medicine
Nathan Dow, Julia R. Coleman, Hunter Moore, Zachary T. Osborn, Adrian M. Sackheim, Grant Hennig, Saulius Butenas, Mark T. Nelson, Ernest E. Moore, Kalev Freeman
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
(2020)
Article
Peripheral Vascular Disease
Adam S. Greenstein, Sharifah Zamiah Abdul Syed Kadir, Viktoria Csato, Sarah A. Sugden, Rachael A. Baylie, David A. Eisner, Mark T. Nelson
Article
Cardiac & Cardiovascular Systems
Julien Ratelade, Nicholas R. Klug, Damiano Lombardi, Monara Kaelle Servulo Cruz Angelim, Fabrice Dabertrand, Valerie Domenga-Denier, Rustam Al-Shahi Salman, Colin Smith, Jean-Frederic Gerbeau, Mark T. Nelson, Anne Joutel
Article
Multidisciplinary Sciences
Guiling Zhao, Humberto C. Joca, Mark T. Nelson, W. Jonathan Lederer
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Arash Moshkforoush, Baarbod Ashenagar, Osama F. Harraz, Fabrice Dabertrand, Thomas A. Longden, Mark T. Nelson, Nikolaos M. Tsoukias
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Osama F. Harraz, David Hill-Eubanks, Mark T. Nelson
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biology
Colin M. Cleary, Thiago S. Moreira, Ana C. Takakura, Mark T. Nelson, Thomas A. Longden, Daniel K. Mulkey
Article
Biochemistry & Molecular Biology
Maria Sancho, Nicholas R. Klug, Amreen Mughal, Masayo Koide, Saul Huerta de la Cruz, Thomas J. Heppner, Adrian D. Bonev, David Hill-Eubanks, Mark T. Nelson
Summary: The presence of K-ATP channels in the capillary endothelial cells and pericytes plays a crucial role in regulating cerebral blood flow.
Article
Multidisciplinary Sciences
Jade L. Taylor, Harry A. T. Pritchard, Katy R. Walsh, Patrick Strangward, Claire White, David Hill-Eubanks, Mariam Alakrawi, Grant W. Hennig, Stuart M. Allan, Mark T. Nelson, Adam S. Greenstein
Summary: The study investigates the role of vasodilatory pathways in cerebral arteries in the context of Alzheimer's disease. The researchers found that dysfunction in potassium channels involved in vasodilation may contribute to reduced blood flow and impaired functional hyperemia, highlighting the importance of targeting these pathways for potential therapeutic interventions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Neurosciences
Amreen Mughal, Mark T. Nelson, David Hill-Eubanks
Summary: The brain's high energy demand is met by neurovascular coupling mechanisms that link neuronal activity with increased blood delivery. These mechanisms have shifted focus to capillary-level processes, revealing a regulatory role of the post-arteriole transition zone and the contribution of perivascular mural cells to blood distribution control.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Physiology
Viktoria Csato, Sharifah Z. S. A. Kadir, Kaivan Khavandi, Hayley Bennett, Sarah Sugden, Alison M. Gurney, Harry T. Pritchard, David Hill-Eubanks, Philip Eaton, Mark T. Nelson, Adam S. Greenstein
PHYSIOLOGICAL REPORTS
(2019)