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https://www.readbyqxmd.com/read/29338006/a-model-for-cooperative-gating-of-l-type-ca2-channels-and-its-effects-on-cardiac-alternans-dynamics
#1
Daisuke Sato, Rose E Dixon, Luis F Santana, Manuel F Navedo
In ventricular myocytes, membrane depolarization during the action potential (AP) causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which trigger the release of calcium (Ca2+) from the sarcoplasmic reticulum (SR). This results in an increase in intracellular Ca2+ (Cai) that initiates contraction. During pulsus alternans, cardiac contraction is unstable, going from weak to strong in successive beats despite a constant heart rate. These cardiac alternans can be caused by the instability of membrane potential (Vm) due to steep AP duration (APD) restitution (Vm-driven alternans), instability of Cai cycling (Ca2+-driven alternans), or both, and may be modulated by functional coupling between clustered CaV1...
January 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29337261/heart-rate-variability-alters-cardiac-repolarization-and-electromechanical-dynamics
#2
Vrishti M Phadumdeo, Seth H Weinberg
Heart rate continuously varies due to autonomic regulation, stochasticity in pacemaking, and circadian rhythm, collectively termed heart rate variability (HRV), during normal physiological conditions. Low HRV is clinically associated with an elevated risk of cardiac arrhythmias. Alternans, a beat-to-beat alternation in action potential duration (APD) and/or intracellular calcium (Ca) transient, is a well-known risk factor associated with cardiac arrhythmias that is typically studied under conditions of a constant pacing rate, i...
January 11, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29333726/calcium-current-properties-in-dystrophin-deficient-ventricular-cardiomyocytes-from-aged-mdx-mice
#3
Lena Rubi, Hannes Todt, Helmut Kubista, Xaver Koenig, Karlheinz Hilber
Duchenne muscular dystrophy (DMD), caused by mutations in the gene encoding for the cytoskeletal protein dystrophin, is linked with severe cardiac complications including cardiomyopathy development and cardiac arrhythmias. We and others recently reported that currents through L-type calcium (Ca) channels were significantly increased, and channel inactivation was reduced in dystrophin-deficient ventricular cardiomyocytes derived from the mdx mouse, the most commonly used animal model for human DMD. These gain-of-function Ca channel abnormalities may enhance the risk of Ca-dependent arrhythmias and cellular Ca overload in the dystrophic heart...
January 2018: Physiological Reports
https://www.readbyqxmd.com/read/29330129/estradiol-up-regulates-l-type-ca2-channels-via-membrane-bound-estrogen-receptor-phosphoinositide-3kinase-akt-camp-response-element-binding-protein-signaling-pathway
#4
Xiaoyan Yang, Xiaofang Mao, Gao Xu, Shasha Xing, Ansuman Chattopadhyay, Si Jin, Guy Salama
BACKGROUND: In long QT type-2 (LQT2), women are more prone to lethal arrhythmias called Torsade de Pointes (TdP) than men. We previously reported that 17-β-estradiol (E2) upregulates L-type Ca2+-channels and current (ICa,L) (∼30%) in rabbit ventricular myocytes by a classical genomic-mechanism mediated by estrogen-receptor-α (ER)α. In LQT2 ( IKr-blockade or bradycardia), the higher Ca2+ influx via ICa,L, causes Ca2+-overload, spontaneous sarcoplasmic reticulum Ca2+-release, and re-activation of ICa,L that trigger early afterdepolarizations (EADs) and TdP...
January 9, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29318456/voltage-dependence-of-the-ca2-transient-in-endocardial-and-epicardial-myocytes-from-the-left-ventricle-of-goto-kakizaki-type-2-diabetic-rats
#5
Lina Al Kury, Vadym Sydorenko, Manal M A Smail, Muhammad Anwar Qureshi, Anatoliy Shmygol, Murat Oz, Jaipaul Singh, Frank Christopher Howarth
Diabetes mellitus is a major global health disorder and, currently, over 450 million people have diabetes with 90% suffering from type 2 diabetes. Left untreated, diabetes may lead to cardiovascular diseases which are a leading cause of death in diabetic patients. Calcium is the trigger and regulator of cardiac muscle contraction and derangement in cellular Ca2+ homeostasis, which can result in heart failure and sudden cardiac death. It is of paramount importance to investigate the regional involvement of Ca2+ in diabetes-induced cardiomyopathy...
January 9, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29316265/effects-of-chronic-hypoxia-on-diaphragm-function-in-deer-mice-native-to-high-altitude
#6
Neal J Dawson, Sulayman A Lyons, Danielle A Henry, Graham R Scott
AIM: We examined the effects of chronic hypoxia on diaphragm function in high- and low-altitude populations of Peromyscus mice. METHODS: Deer mice (P. maniculatus) native to high altitude and congeneric mice native to low altitude (P. leucopus) were born and raised in captivity to adulthood, and were acclimated to normoxia or hypobaric hypoxia (12 or 9 kPa, simulating hypoxia at 4300 m and 7000 m) for 6-8 weeks. We then measured indices of mitochondrial respiration capacity, force production, and fatigue resistance in the diaphragm...
January 9, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29315676/aging-impairs-regulation-of-ryanodine-receptors-from-edl-but-not-soleus-muscles
#7
Angela J Gaboardi, Jochen Kressler, Teresa K Snow, Edward M Balog
INTRODUCTION: Because impaired excitation-contraction coupling and reduced sarcoplasmic reticulum Ca2+ release may contribute to the age-associated decline in skeletal muscle strength, we investigated the effect of aging on RyR1 regulation by physiological channel ligands. METHODS: [3 H]Ryanodine binding to membranes from 8 and 26 month old Fischer 344 extensor digitorum longus (EDL) and soleus muscles was used to investigate the effects of age on RyR1 modulation by Ca2+ and calmodulin (CaM)...
January 9, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29306925/calcium-sensitization-mechanisms-in-detrusor-smooth-muscles
#8
REVIEW
Irfan Anjum
The contraction of detrusor smooth muscles depends on the increase in intracellular calcium. The influx of calcium from the plasma membrane calcium channels and calcium release from the sarcoplasmic reticulum give rise to intracellular calcium. Under the pathophysiological conditions, the increased sensitivity of regulatory and contractile proteins to calcium also plays an important role in maintaining the spontaneous detrusor smooth muscle activity. Many proteins have been identified to play a role in calcium sensitization...
January 8, 2018: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29304851/development-of-the-excitation-contraction-coupling-machinery-and-its-relation-to-myofibrillogenesis-in-human-ipsc-derived-skeletal-myocytes
#9
Jeanne Lainé, Gunnar Skoglund, Emmanuel Fournier, Nacira Tabti
BACKGROUND: Human induced pluripotent stem cells-derived myogenic progenitors develop functional and ultrastructural features typical of skeletal muscle when differentiated in culture. Besides disease-modeling, such a system can be used to clarify basic aspects of human skeletal muscle development. In the present study, we focus on the development of the excitation-contraction (E-C) coupling, a process that is essential both in muscle physiology and as a tool to differentiate between the skeletal and cardiac muscle...
January 5, 2018: Skeletal Muscle
https://www.readbyqxmd.com/read/29302020/muscle-function-decline-and-mitochondria-changes-in-middle-age-precede-sarcopenia-in-mice
#10
Andrea Del Campo, Ignacio Contreras-Hernández, Mauricio Castro-Sepúlveda, Cristian A Campos, Reinaldo Figueroa, María Florencia Tevy, Verónica Eisner, Mariana Casas, Enrique Jaimovich
Sarcopenia is the degenerative loss of muscle mass and strength with aging. Although a role of mitochondrial metabolism in muscle function and in the development of many diseases has been described, the role of mitochondrial topology and dynamics in the process of muscle aging is not fully understood. This work shows a time line of changes in both mitochondrial distribution and skeletal muscle function during mice lifespan. We isolated muscle fibers from flexor digitorum brevis of mice of different ages. A fusion-like phenotype of mitochondria, together with a change in orientation perpendicular to the fiber axis was evident in the Adult group compared to Juvenile and Older groups...
January 4, 2018: Aging
https://www.readbyqxmd.com/read/29289652/cellular-mechanisms-of-metabolic-syndrome-related-atrial-decompensation-in-a-rat-model-of-hfpef
#11
Felix Hohendanner, David Bode, Uwe Primessnig, Tim Guthof, Rafael Doerr, Sarah Jeuthe, Sophie Reimers, Kun Zhang, Doris Bach, Paulina Wakula, Burkert M Pieske, Frank R Heinzel
Heart failure (HF) with preserved ejection fraction (HFpEF) is present in about 50% of HF patients. Atrial remodeling is common in HFpEF and associated with increased mortality. We postulate that atrial remodeling is associated with atrial dysfunction in vivo related to alterations in cardiomyocyte Calcium (Ca) signaling and remodeling. We examined atrial function in vivo and Ca transients (CaT) (Fluo4-AM, field stim) in atrial cardiomyocytes of ZSF-1 rats without (Ln; lean hypertensive) and with metabolic syndrome (Ob; obese, hypertensive, diabetic) and HFpEF...
December 28, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29289553/advanced-aging-causes-diaphragm-functional-abnormalities-global-proteome-remodeling-and-loss-of-mitochondrial-cysteine-redox-flexibility-in-mice
#12
Rachel C Kelley, Brian McDonagh, Leonardo F Ferreira
AIM: Inspiratory muscle (diaphragm) function declines with age, contributing to exercise intolerance and impaired airway clearance. Studies of diaphragm dysfunction in rodents have focused on moderate aging (~24months); thus, the impact of advanced age on the diaphragm and potential mechanisms of dysfunction are less clear. Therefore, we aimed to define the effects of advanced age on the mechanics, morphology, and global and redox proteome of the diaphragm. METHODS: We studied diaphragm from young (6months) and very old male mice (30months)...
December 28, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29284662/junctional-trafficking-and-restoration-of-retrograde-signaling-by-the-cytoplasmic-ryr1-domain
#13
Alexander Polster, Stefano Perni, Dilyana Filipova, Ong Moua, Joshua D Ohrtman, Hicham Bichraoui, Kurt G Beam, Symeon Papadopoulos
The type 1 ryanodine receptor (RyR1) in skeletal muscle is a homotetrameric protein that releases Ca2+ from the sarcoplasmic reticulum (SR) in response to an "orthograde" signal from the dihydropyridine receptor (DHPR) in the plasma membrane (PM). Additionally, a "retrograde" signal from RyR1 increases the amplitude of the Ca2+ current produced by CaV1.1, the principle subunit of the DHPR. This bidirectional signaling is thought to depend on physical links, of unknown identity, between the DHPR and RyR1. Here, we investigate whether the isolated cytoplasmic domain of RyR1 can interact structurally or functionally with CaV1...
December 28, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29278865/simvastatin-activates-single-skeletal-ryr1-channels-but-exerts-more-complex-regulation-of-the-cardiac-ryr2-isoform
#14
Elisa Venturi, Chris Lindsay, Sabine Lotteau, Zhaokang Yang, Emma Steer, Katja Witschas, Abigail D Wilson, James R Wickens, Angela J Russell, Derek Steele, Sarah Calaghan, Rebecca Sitsapesan
BACKGROUND AND PURPOSE: Statins are amongst the most widely prescribed drugs for those at risk of cardiovascular disease, lowering cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Although effective in prevention of cardiovascular disease, statin use is associated with muscle weakness, myopathies and, in rare cases, fatal rhabdomyolysis. As simvastatin, a commonly prescribed statin, can promote Ca2+ release from sarcoplasmic reticulum (SR) vesicles, we investigated if simvastatin could directly activate skeletal (RyR1) and cardiac (RyR2) ryanodine receptors...
December 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29259040/small-ca2-releases-enable-hour-long-high-frequency-contractions-in-midshipman-swimbladder-muscle
#15
Frank E Nelson, Stephen Hollingworth, James O Marx, Stephen M Baylor, Lawrence C Rome
Type I males of the Pacific midshipman fish (Porichthys notatus) vibrate their swimbladder to generate mating calls, or "hums," that attract females to their nests. In contrast to the intermittent calls produced by male Atlantic toadfish (Opsanus tau), which occur with a duty cycle (calling time divided by total time) of only 3-8%, midshipman can call continuously for up to an hour. With 100% duty cycles and frequencies of 50-100 Hz (15°C), the superfast muscle fibers that surround the midshipman swimbladder may contract and relax as many as 360,000 times in 1 h...
December 19, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29248564/el20-a-potent-antiarrhythmic-compound-selectively-inhibits-calmodulin-deficient-ryanodine-receptor-type-2
#16
Robert C Klipp, Na Li, Qiongling Wang, Tarah A Word, Martha Sibrian-Vazquez, Robert M Strongin, Xander H T Wehrens, Jonathan J Abramson
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disorder caused by mutations in the cardiac ryanodine receptor (RyR2) that increase diastolic Ca2+ leak from the sarcoplasmic reticulum (SR). Calmodulin (CaM) dissociation from RyR2 has been associated with diastolic Ca2+ leak in heart failure. OBJECTIVE: Determine if tetracaine-derivative, EL20, inhibits abnormal Ca2+ release from RyR2 in a CPVT model and the underlying mechanism of inhibition...
December 14, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29247050/voltage-modulates-halothane-triggered-ca2-release-in-malignant-hyperthermia-susceptible-muscle
#17
Alberto Zullo, Martin Textor, Philipp Elischer, Stefan Mall, Andreas Alt, Werner Klingler, Werner Melzer
Malignant hyperthermia (MH) is a fatal hypermetabolic state that may occur during general anesthesia in susceptible individuals. It is often caused by mutations in the ryanodine receptor RyR1 that favor drug-induced release of Ca2+ from the sarcoplasmic reticulum. Here, knowing that membrane depolarization triggers Ca2+ release in normal muscle function, we study the cross-influence of membrane potential and anesthetic drugs on Ca2+ release. We used short single muscle fibers of knock-in mice heterozygous for the RyR1 mutation Y524S combined with microfluorimetry to measure intracellular Ca2+ signals...
December 15, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29239839/the-formin-diaph1-is-a-key-modulator-of-myocardial-ischemia-reperfusion-injury
#18
Karen M O'Shea, Radha Ananthakrishnan, Qing Li, Nosirudeen Quadri, Devi Thiagarajan, Gopalkrishna Sreejit, Lingjie Wang, Hylde Zirpoli, Juan Francisco Aranda, Arthur S Alberts, Ann Marie Schmidt, Ravichandran Ramasamy
The biochemical, ionic, and signaling changes that occur within cardiomyocytes subjected to ischemia are exacerbated by reperfusion; however, the precise mechanisms mediating myocardial ischemia/reperfusion (I/R) injury have not been fully elucidated. The receptor for advanced glycation end-products (RAGE) regulates the cellular response to cardiac tissue damage in I/R, an effect potentially mediated by the binding of the RAGE cytoplasmic domain to the diaphanous-related formin, DIAPH1. The aim of this study was to investigate the role of DIAPH1 in the physiological response to experimental myocardial I/R in mice...
November 21, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29236992/the-effects-of-aging-on-the-regulation-of-t-tubular-ica-by-caveolin-in-mouse-ventricular-myocytes
#19
Cherrie H T Kong, Simon M Bryant, Judy J Watson, Hanne C Gadeberg, David M Roth, Hemal H Patel, Mark B Cannell, Clive H Orchard, Andrew F James
Aging is associated with diminished cardiac function in males. Cardiac excitation-contraction coupling in ventricular myocytes involves Ca influx via the Ca current (ICa) and Ca release from the sarcoplasmic reticulum, which occur predominantly at t-tubules. Caveolin-3 regulates t-tubular ICa, partly through PKA, and both ICa and caveolin-3 decrease with age. We therefore investigated ICa and t-tubule structure and function in cardiomyocytes from male WT and caveolin-3-overexpressing (Cav-3OE) mice at 3 and 24 months of age...
December 9, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29235522/an-optogenetic-arrhythmia-model-to-study-catecholaminergic-polymorphic-ventricular-tachycardia-mutations
#20
Elisabeth Fischer, Alexander Gottschalk, Christina Schüler
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition of abnormal heart rhythm (arrhythmia), induced by physical activity or stress. Mutations in ryanodine receptor 2 (RyR2), a Ca2+ release channel located in the sarcoplasmic reticulum (SR), or calsequestrin 2 (CASQ2), a SR Ca2+ binding protein, are linked to CPVT. For specific drug development and to study distinct arrhythmias, simple models are required to implement and analyze such mutations. Here, we introduced CPVT inducing mutations into the pharynx of Caenorhabditis elegans, which we previously established as an optogenetically paced heart model...
December 13, 2017: Scientific Reports
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