Review
Physiology
Andras Varro, Jakub Tomek, Norbert Nagy, Laszlo Virag, Elisa Passini, Blanca Rodriguez, Istvan Baczko
Summary: Cardiac arrhythmias often stem from changes in the electro-physiological properties of cardiac cells and their ionic mechanisms. Understanding the pathophysiology of human cellular electrophysiology can aid in developing novel antiarrhythmic strategies.
PHYSIOLOGICAL REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Matthew D. McCoy, Aman Ullah, W. Jonathan Lederer, M. Saleet Jafri
Summary: Mutations in the calcium-sensing protein calmodulin (CaM) can cause cardiac arrhythmia diseases, Long QT Syndrome 14 (LQT14) and Catecholaminergic Polymorphic Ventricular Tachycardia Type 4 (CPVT4), with different severities. The CaM mutants associated with LQT14 disrupt the calcium-dependent inactivation of the L-Type calcium channel (LCC), while CPVT4 mutants have changes in their affinity to the ryanodine receptor. Simulations in a model for excitation-contraction coupling show that LQT14 variants can lead to a CPVT4 phenotype under certain conditions. These findings emphasize the importance of calcium-dependent inactivation in heart function.
Review
Biology
Carol Ann Remme
Summary: The influx of sodium ions through voltage-gated sodium channels is crucial for proper electrical conduction in the heart. Dysfunction of sodium channels can lead to life-threatening arrhythmias in acquired conditions and inherited disorders. Recent research has revealed the complex nature of sodium channel distribution and function, as well as its impact on cardiac structural integrity. Moreover, sodium channels and their role in various extracardiac tissues are being increasingly recognized. This review provides an overview of these novel insights and their contribution to our understanding of sodium channelopathies and dysfunction.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Review
Cell Biology
Tanawat Attachaipanich, Siriporn C. Chattipakorn, Nipon Chattipakorn
Summary: This review summarizes the current available evidence regarding the potential benefits of SGLT-2 inhibitors against cardiac arrhythmias, ranging from basic research to clinical reports. It comprehensively examines the effects of SGLT-2 inhibitors on cardiac action potential, cellular ion currents, calcium ion homeostasis, and cardiac mitochondrial function, as well as the association with arrhythmias such as atrial fibrillation and ventricular arrhythmias.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Pei Wang, Shangcheng Xu, Jiqian Xu, Yanguo Xin, Yan Lu, Huiliang Zhang, Bo Zhou, Haodong Xu, Shey-Shing Sheu, Rong Tian, Wang Wang
Summary: This study reveals that chronic stress can upregulate the expression of mitochondrial calcium uniporter (MCU), preserving calcium homeostasis and cardiomyocyte viability to counteract stress-induced pathological cardiac remodeling.
Article
Cardiac & Cardiovascular Systems
Loryn J. Bohne, Hailey J. Jansen, Tristan W. Dorey, Irene M. Daniel, K. Lockhart Jamieson, Darrell D. Belke, Megan D. Mcrae, Robert A. Rose
Summary: This study demonstrates that GLP-1 and its analogues can reduce the incidence of atrial fibrillation and prevent atrial remodeling in patients with type 2 diabetes.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2023)
Article
Biology
Yan Zou, Miaomiao Zhang, Qiongfeng Wu, Ning Zhao, Minwei Chen, Cui Yang, Yimei Du, Bing Han
Summary: This study demonstrates that TRPV4 activation contributes to pressure overload-induced cardiac hypertrophy and dysfunction through the Ca2+/CaMKII mediated activation of NF kappa B-NLRP3. Therefore, TRPV4 may represent a potential therapeutic drug target for cardiac hypertrophy and dysfunction after pressure overload.
Article
Cell Biology
Michele Bevere, Caterina Morabito, Simone Guarnieri, Maria A. Mariggio
Summary: This study investigated the impact of GAP43 on cardiac tissue and found that its absence led to morphological changes and signs of hypertrophy in the hearts of knockout mice. This suggests that GAP43 may play a significant role in the functional processes of cardiac muscle.
HISTOCHEMISTRY AND CELL BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Masayuki Takahashi, Hisashi Yokoshiki, Hirofumi Mitsuyama, Masaya Watanabe, Taro Temma, Rui Kamada, Hikaru Hagiwara, Yumi Takahashi, Toshihisa Anzai
Summary: The study demonstrates that the blocker apamin, which targets small-conductance Ca2+-activated K+ channels, has anti-arrhythmic effects by improving action potential duration shortening and calcium handling abnormalities in ventricular myocardium. This effect is likely attributed to the reduction of Ca-i/V-m uncoupling.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Monica Gallego, Julian Zayas-Arrabal, Amaia Alquiza, Beatriz Apellaniz, Oscar Casis
Summary: Diabetes is a chronic metabolic disease with hyperglycemia, and cardiovascular disease is a major complication leading to mortality in diabetic patients. Diabetic cardiomyopathy causes abnormal heart function and electrical remodeling, including prolonged QT interval, increasing the risk of life-threatening ventricular arrhythmias. New antidiabetic drugs must undergo thorough cardiovascular evaluation to reduce the risk of arrhythmia and sudden death in diabetic patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Po Wei Kang, Nourdine Chakouri, Johanna Diaz, Gordon F. Tomaselli, David T. Yue, Manu Ben-Johny
Summary: The action of calmodulin on NaV1.5 channels is crucial for the occurrence of arrhythmias. Disruption of Ca2+-free CaM preassociation with NaV1.5 results in a decrease in peak open probability and an increase in persistent NaV openings, altering the inactivation mechanism of NaV1.5.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Medicine, Research & Experimental
Kexin Ma, Guoping Ma, Zijing Guo, Gang Liu, Wenjie Liang
Summary: Ventricular arrhythmia (VA) is a highly fatal arrhythmia involving multiple ion channels, and activated CaMKII plays a key role in this condition by regulating ion channels in the heart. Understanding the mechanisms of VA based on the CaMKII pathway is crucial for clinical treatment and drug development.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Dorothee Jakob, Alexander Klesen, Benoit Allegrini, Elisa Darkow, Diana Aria, Ramona Emig, Ana Simon Chica, Eva A. Rog-Zielinska, Tim Guth, Friedhelm Beyersdorf, Fabian A. Kari, Susanne Proksch, Stephane N. Hatem, Matthias Karck, Stephan R. Kunzel, Helene Guizouarn, Constanze Schmidt, Peter Kohl, Ursula Ravens, Remi Peyronnet
Summary: The study found that human atrial fibroblasts contain at least two types of ion channels activated during stretch: Piezol and BKca. Sustained atrial fibrillation is associated with increased Piezol and decreased BKca activity, indicating differential regulation of these channels.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Clinical Neurology
Ming S. Soh, Richard D. Bagnall, Christopher Semsarian, Ingrid E. Scheffer, Samuel F. Berkovic, Christopher A. Reid
Summary: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death in epilepsy. This study found that SCN5A arrhythmogenic variants may confer increased risk of sudden death in individuals with epilepsy.
Review
Neurosciences
Andy Pironet, Frone Vandewiele, Rudi Vennekens
Summary: Cardiac arrhythmias pose a significant health threat, but are difficult to predict, prevent, and treat. Disturbed Ca2+ homeostasis in cardiac muscle cells has been identified as a key mechanism in the occurrence of arrhythmias. TRPM4, a Ca2+-activated channel, has been linked to Ca2+-induced arrhythmias, contributing to membrane depolarisation and increased excitability. Evidence from genetically modified mice, human patient mutations, and a TRPM4 blocking compound support this hypothesis. This overview provides insights into our understanding of Ca2+-dependent arrhythmias.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Cell Biology
Zsuzsanna Gaal, Janos Fodor, Attila Olah, Tamas Radovits, Bela Merkely, Janos Magyar, Laszlo Csernoch
Summary: Studies on the changes in microRNA expression in skeletal muscle after chronic swim training suggest that these changes contribute to an improved metabolic profile in skeletal muscle, which may have a positive impact on the prevention of chronic civilization diseases.
JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY
(2022)
Article
Chemistry, Medicinal
Csaba Dienes, Zsigmond Mate Kovacs, Tamas Hezso, Janos Almassy, Janos Magyar, Tamas Banyasz, Peter P. Nanasi, Balazs Horvath, Norbert Szentandrassy
Summary: TRPM4 is a member of the TRPM protein family that regulates membrane potential and Ca2+ homeostasis. It is widely expressed in multiple organs and involved in various physiological functions, as well as contributing to pathological conditions.
Article
Chemistry, Medicinal
Zsigmond Mate Kovacs, Csaba Dienes, Tamas Hezso, Janos Almassy, Janos Magyar, Tamas Banyasz, Peter P. Nanasi, Balazs Horvath, Norbert Szentandrassy
Summary: This review discusses the pharmacological modulation of TRPM4, as well as the methods and functions of studying TRPM4.
Review
Biochemistry & Molecular Biology
Norbert Szentandrassy, Zsuzsanna E. Magyar, Judit Hevesi, Tamas Banyasz, Peter P. Nanasi, Janos Almassy
Summary: Cardiac diseases are a leading cause of death worldwide, and understanding the molecular pathomechanisms and identifying new therapeutic targets is crucial in cardiac research. The cardiac ryanodine receptor (RyR2) is believed to be a promising therapeutic target in certain heart diseases known as cardiac ryanopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Physiology
Balazs Horvath, Norbert Szentandrassy, Csaba Dienes, Zsigmond M. Kovacs, Peter P. Nanasi, Ye Chen-Izu, Leighton T. Izu, Tamas Banyasz
Summary: The patch clamp technique has undergone continuous advancement in cardiac electrophysiology, allowing for the recording of multiple currents under various command pulses. Its potential applications in integrative physiology are highlighted in this review.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Norbert Nagy, Noemi Toth, Peter P. Nanasi
Summary: Experimental results suggest that Na+/Ca2+ exchanger inhibition using novel highly selective inhibitors may help increase Ca2+ levels, decrease arrhythmogenic depolarizations, and reduce excessive Ca2+ influx.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Arnold Peter Raduly, Fruzsina Sarkany, Mate Balazs Kovacs, Brigitta Bernat, Bela Juhasz, Zoltan Szilvassy, Robert Porszasz, Balazs Horvath, Norbert Szentandrassy, Peter Nanasi, Zoltan Csanadi, Istvan Edes, Attila Toth, Zoltan Papp, Daniel Priksz, Attila Borbely
Summary: Recent cardiotropic drug developments have focused on cardiac myofilaments, and danicamtiv, as the second direct myosin activator, has shown promising results in the treatment of heart failure with reduced ejection fraction. In vitro and in vivo studies have demonstrated that danicamtiv improves systolic function but may also limit diastolic performance at higher concentrations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Zsigmond Mate Kovacs, Jozsef Ovari, Csaba Dienes, Janos Magyar, Tamas Banyasz, Peter P. Nanasi, Balazs Horvath, Adam Feher, Zoltan Varga, Norbert Szentandrassy
Summary: ABT-333, an antiviral agent used in hepatitis C treatment, may pose a risk of arrhythmia due to its methanesulfonamide group. It was found that ABT-333 can reduce ion currents and action potentials in myocardial cells, leading to an increase in early plateau potential and occurrence of abnormal action potentials in some cells. However, considering its therapeutic plasma concentration, the risk of arrhythmia with ABT-333 is very low even in case of drug overdose.
Article
Chemistry, Medicinal
Balazs Horvath, Zsigmond Kovacs, Csaba Dienes, Jozsef Ovari, Norbert Szentandrassy, Janos Magyar, Tamas Banyasz, Andras Varro, Peter P. Nanasi
Summary: The characteristics of late sodium current (I-Na,I-late) and its conductance changes (G(Na,late)) were studied in rabbit, canine, and guinea pig ventricular myocytes. The gating kinetics of I-Na,I-late showed notable interspecies differences, which cannot be explained by differences in action potential morphology. Intracellular Ca2+ concentration and Anemonia sulcata (ATX-II) toxin also influenced the I-Na,I-late and G(Na,late) profiles differently in canine and guinea pig myocytes.