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https://www.readbyqxmd.com/read/29030236/long-term-aerobic-exercise-in-calsequestrin2-knockout-mice-accentuates-vagal-antagonism-during-%C3%AE-adrenergic-stimulation-which-restricts-heart-rate-acceleration-and-paradoxically-increases-abnormal-ryanodine-receptor-calcium-leak-in-ventricular-myocytes
#1
Hsiang-Ting Ho, Senthil Thambidorai, Björn C Knollmann, George E Billman, Sandor Györke, Anuradha Kalyanasundaram
BACKGROUND: Long-term aerobic exercise (EX) alters autonomic balance which may not be favorable in heart rate (HR) dependent arrhythmic diseases including Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) due to preexisting bradycardia and increased sensitivity to parasympathetic stimulation. OBJECTIVE: The purpose of this study was to determine if long-term exercise-induced autonomic adaptations modify CPVT susceptibility. METHODS: We determined exercise-induced parasympathetic effects on HR, arrhythmia incidence and intracellular sarcoplasmic reticulum (SR) Ca(2+) leak in atrial (ACM) and ventricular (VCM) cardiomyocytes, in EX Calsequestrin knockout (CASQ2(-/-)) mice, a model of CPVT...
October 10, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29029787/early-testosterone-replacement-attenuates-intracellular-calcium-dyshomeostasis-in-the-heart-of-testosterone-deprived-male-rats
#2
Punate Weerateerangkul, Krekwit Shinlapawittayatorn, Siripong Palee, Nattayaporn Apaijai, Siriporn C Chattipakorn, Nipon Chattipakorn
BACKGROUND: Testosterone deficiency in elderly men increases the risk of cardiovascular disease. In bilateral orchiectomized (ORX) animals, impaired cardiac Ca(2+) regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important role of testosterone in cardiac Ca(2+) regulation. However, the temporal changes of Ca(2+) dyshomeostasis in testosterone-deprived conditions are unclear. Moreover, the effects of early vs. late testosterone replacement are unknown...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29027245/epac-induced-ryanodine-receptor-type-2-activation-inhibits-sodium-currents-in-atrial-and-ventricular-murine-cardiomyocytes
#3
Haseeb Valli, Shiraz Ahmad, Sujan Sriharan, Lydia D Dean, Andrew A Grace, Kamalan Jeevaratnam, Hugh R Matthews, Christopher L-H Huang
Acute RyR2 activation by exchange protein directly activated by cAMP (Epac) reversibly perturbs myocyte Ca(2+) homeostasis, slows myocardial action potential conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies, preserving in vivo extracellular and intracellular conditions, investigated Na(+) current in intact cardiomyocytes in murine atrial and ventricular preparations following Epac activation. Depolarising steps to varying test voltages activated typical voltage-dependent Na(+) currents...
October 12, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29023089/gelatin-polyaniline-composite-nanofibers-enhanced-excitation-contraction-coupling-system-maturation-in-myotubes
#4
Serge Ostrovidov, Majid Ebrahimi, Hojae Bae, Hung Kim Nguyen, Sahar Salehi, Sang Bok Kim, Akichika Kumatani, Tomokazu Matsue, Xuetao Shi, Ken Nakajima, Shizu Hidema, Makoto Osanai, Ali Khademhosseini
In this study, composite gelatin-polyaniline (PANI) nanofibers doped with camphorsulfonic acid (CSA) was fabricated by electrospinning and used as substrates to culture C2C12 myoblast cells. We observed enhanced myotube formation on composite gelatin-PANI nanofibers compared to gelatin nanofibers, concomitantly with enhanced myotube maturation. Thus, in myotubes, intracellular organization, co-localization of the dihydropyridine receptor (DHPR) and ryanodine receptor (RyR), expression of genes correlated to the excitation-contraction (E-C) coupling apparatus, calcium transients, and myotube contractibility were increased...
October 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28993151/using-a-smalp-platform-to-determine-a-sub-nm-single-particle-cryo-em-membrane-protein-structure
#5
Mayuriben Parmar, Shaun Rawson, Charlotte A Scarff, Adrian Goldman, Timothy R Dafforn, Stephen P Muench, Vincent L G Postis
The field of membrane protein structural biology has been revolutionized over the last few years with a number of high profile structures being solved using cryo-EM including Piezo, Ryanodine receptor, TRPV1 and the Glutamate receptor. Further developments in the EM field hold the promise of even greater progress in terms of greater resolution, which for membrane proteins is still typically within the 4-7Å range. One advantage of a cryo-EM approach is the ability to study membrane proteins in more "native" like environments for example proteoliposomes, amphipols and nanodiscs...
October 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28993142/ghrelin-upregulates-the-phosphorylation-of-the-glun2b-subunit-of-the-nmda-receptor-by-activating-ghsr1a-and-fyn-in-the-rat-hippocampus
#6
Liza Berrout, Masako Isokawa
Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation. This increase was independent of GluN2B subunit activity or NMDAR channel activity...
October 6, 2017: Brain Research
https://www.readbyqxmd.com/read/28988521/the-cardioprotective-effect-of-rosmarinic-acid-on-acute-myocardial-infarction-and-genes-involved-in-ca-2-homeostasis
#7
Somayeh Javidanpour, Mahin Dianat, Mohammad Badavi, Seyyed Ali Mard
Acute myocardial infarction (AMI) is a common cause of hospitalization and high mortality due to lethal arrhythmias. Sarcoplasmic reticulum Ca(2+) ATPase (sarcoplasmic reticulum Ca(2+) ATPase (SERCA)2) and ryanodine receptor (ryanodine receptor (RyR)2) regulate the cytosolic Ca(2+) ion concentration. Rosmarinic acid (RA) is one of the most common caffeic esters in Rosmarinus officinalis. The present study was conducted to test the hypothesis whether RA can protect cardiac function against AMI and arrhythmias induced by isoproterenol through the regulatory effect of SERCA2 and RyR2 gene expression...
October 8, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28974554/thyroid-and-glucocorticoid-hormones-promote-functional-t-tubule-development-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#8
Shan S Parikh, Daniel J Blackwell, Nieves Gomez-Hurtado, Michael Frisk, Lili Wang, Kyungsoo Kim, Christen P Dahl, Arnt E Fiane, Theis Tønnessen, Dmytro O Kryshtal, William E Louch, Bjorn C Knollmann
Rationale: Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional maturation of hiPSC-CM including lack of t-tubules, immature excitation-contraction (EC) coupling, and inefficient Ca-induced Ca release (CICR) remain major limitations. Objective: Thyroid and glucocorticoid hormones are critical for heart maturation. We hypothesized that their addition to standard protocols would promote t-tubule development and mature EC coupling of hiPSC-CM when cultured on extracellular matrix with physiological stiffness (Matrigel mattress)...
October 2, 2017: Circulation Research
https://www.readbyqxmd.com/read/28974495/prenatal-hypoxia-induced-dysfunction-in-cerebral-arteries-of-offspring-rats
#9
Jiaqi Tang, Na Li, Xueyi Chen, Qinqin Gao, Xiuwen Zhou, Yingying Zhang, Bailin Liu, Miao Sun, Zhice Xu
BACKGROUND: Hypoxia during pregnancy could cause abnormal development and lead to increased risks of vascular diseases in adults. This study determined angiotensin II (AII)-mediated vascular dysfunction in offspring middle cerebral arteries (MCA). METHODS AND RESULTS: Pregnant rats were subjected to hypoxia. Vascular tension in offspring MCA by AII with or without inhibitors, calcium channel activities, and endoplasmic reticulum calcium stores were tested. Whole-cell patch clamping was used to investigate voltage-dependent calcium channel currents...
October 3, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28966144/effects-of-exercise-training-on-excitation-contraction-coupling-calcium-dynamics-and-protein-expression-in-the-heart-of-the-neotropical-fish-brycon-amazonicus
#10
Rafael Zanelli Rissoli, Eliton da Silva Vasconcelos, Francisco Tadeu Rantin, Ana Lúcia Kalinin
Matrinxã (Brycon amazonicus) is a great swimming performance teleost fish from the Amazon basin. However, the possible cardiac adaptations of this ability are still unknown. Therefore, the aim of the present work was to investigate the effects of prolonged exercise (EX group - 60days under 0.4BL·s(-1)) on ventricular contractility by (i) in-vitro analysis of contractility comparing the relative roles of sodium/calcium exchanger (NCX) and sarcoplasmic reticulum (SR) in the excitation-contraction (E-C) coupling and (ii) molecular analysis of NCX, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) and phospholamban (PLB) expression and quantification...
September 29, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28964152/minimal-model-for-calcium-alternans-due-to-sr-release-refractoriness
#11
Inma R Cantalapiedra, Enrique Alvarez-Lacalle, Angelina Peñaranda, Blas Echebarria
In the heart, rapid pacing rates may induce alternations in the strength of cardiac contraction, termed pulsus alternans. Often, this is due to an instability in the dynamics of the intracellular calcium concentration, whose transients become larger and smaller at consecutive beats. This alternation has been linked experimentally and theoretically to two different mechanisms: an instability due to (1) a strong dependence of calcium release on sarcoplasmic reticulum (SR) load, together with a slow calcium reuptake into the SR or (2) to SR release refractoriness, due to a slow recovery of the ryanodine receptors (RyR2) from inactivation...
September 2017: Chaos
https://www.readbyqxmd.com/read/28964110/a-model-of-cardiac-ryanodine-receptor-gating-predicts-experimental-ca-2-dynamics-and-ca-2-triggered-arrhythmia-in-the-long-qt-syndrome
#12
Dan Wilson, Bard Ermentrout, Jan Němec, Guy Salama
Abnormal Ca(2+) handling is well-established as the trigger of cardiac arrhythmia in catecholaminergic polymorphic ventricular tachycardia and digoxin toxicity, but its role remains controversial in Torsade de Pointes (TdP), the arrhythmia associated with the long QT syndrome (LQTS). Recent experimental results show that early afterdepolarizations (EADs) that initiate TdP are caused by spontaneous (non-voltage-triggered) Ca(2+) release from Ca(2+)-overloaded sarcoplasmic reticulum (SR) rather than the activation of the L-type Ca(2+)-channel window current...
September 2017: Chaos
https://www.readbyqxmd.com/read/28961276/cpvt-associated-cardiac-ryanodine-receptor-mutation-g357s-with-reduced-penetrance-impairs-ca2-release-termination-and-diminishes-protein-expression
#13
Yingjie Liu, Jinhong Wei, Siobhan M Wong King Yuen, Bo Sun, Yijun Tang, Ruiwu Wang, Filip Van Petegem, S R Wayne Chen
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the most lethal inherited cardiac arrhythmias mostly linked to cardiac ryanodine receptor (RyR2) mutations with high disease penetrance. Interestingly, a novel RyR2 mutation G357S discovered in a large family of more than 1400 individuals has reduced penetrance. The molecular basis for the incomplete disease penetrance in this family is unknown. To gain insights into the variable disease expression in this family, we determined the impact of the G357S mutation on RyR2 function and expression...
2017: PloS One
https://www.readbyqxmd.com/read/28951324/modulation-of-cardiac-vagal-tone-by-bradykinin-acting-on-nucleus-ambiguus
#14
Eugen Brailoiu, Matthew McGuire, Shadaria A Shuler, Elena Deliu, Jeffrey L Barr, Mary E Abood, G Cristina Brailoiu
Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. BK produced a dose-dependent increase in cytosolic Ca(2+) concentration. Pretreatment with HOE140, a B2 receptor antagonist, but not with R715, a B1 receptor antagonist, abolished the response to BK...
September 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28942070/ryanodine-receptor-and-fk506-binding-protein-1-in-the-atlantic-killifish-fundulus-heteroclitus-a-phylogenetic-and-population-based-comparison
#15
Erika B Holland, Jared V Goldstone, Isaac N Pessah, Andrew Whitehead, Noah M Reid, Sibel I Karchner, Mark E Hahn, Diane E Nacci, Bryan W Clark, John J Stegeman
Non-dioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine receptors (RyR), microsomal Ca(2+) channels of broad significance. Teleost fish may be important models for NDL PCB neurotoxicity, and we used sequencing databases to characterize teleost RyR and FK506 binding protein 12 or 12.6kDa (genes FKBP1A; FKBP1B), which promote NDL PCB-triggered Ca(2+) dysregulation. Particular focus was placed on describing genes in the Atlantic killifish (Fundulus heteroclitus) genome and searching available RNA-sequencing datasets for single nucleotide variants (SNV) between PCB tolerant killifish from New Bedford Harbor (NBH) versus sensitive killifish from Scorton Creek (SC), MA...
September 4, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28939258/novel-calcium-related-targets-of-insulin-in-hippocampal-neurons
#16
Shaniya Maimaiti, Hilaree N Frazier, Katie L Anderson, Adam O Ghoweri, Lawrence D Brewer, Nada M Porter, Olivier Thibault
Both insulin signaling disruption and Ca(2+) dysregulation are closely related to memory loss during aging and increase the vulnerability to Alzheimer's disease (AD). In hippocampal neurons, aging-related changes in calcium regulatory pathways have been shown to lead to higher intracellular calcium levels and an increase in the Ca(2+)-dependent afterhyperpolarization (AHP), which is associated with cognitive decline. Recent studies suggest that insulin reduces the Ca(2+)-dependent AHP. Given the sensitivity of neurons to insulin and evidence that brain insulin signaling is reduced with age, insulin-mediated alterations in calcium homeostasis may underlie the beneficial actions of insulin in the brain...
September 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28928237/microtubule-structures-underlying-the-sarcoplasmic-reticulum-support-peripheral-coupling-sites-to-regulate-smooth-muscle-contractility
#17
Harry A T Pritchard, Albert L Gonzales, Paulo W Pires, Bernard T Drumm, Eun A Ko, Kenton M Sanders, Grant W Hennig, Scott Earley
Junctional membrane complexes facilitate excitation-contraction coupling in skeletal and cardiac muscle cells by forming subcellular invaginations that maintain close (≤20 nm) proximity of ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR) with voltage-dependent Ca(2+) channels in the plasma membrane. In fully differentiated smooth muscle cells, junctional membrane complexes occur as distributed sites of peripheral coupling. We investigated the role of the cytoskeleton in maintaining peripheral coupling and associated Ca(2+) signaling networks within native smooth muscle cells of mouse and rat cerebral arteries...
September 19, 2017: Science Signaling
https://www.readbyqxmd.com/read/28916620/the-anthracycline-metabolite-doxorubicinol-abolishes-ryr2-sensitivity-to-physiological-changes-in-luminal-ca-2-through-an-interaction-with-calsequestrin
#18
Amy D Hanna, Alexander Lam, Chris Thekkedam, Hermia Willemse, Angela F Dulhunty, Nicole A Beard
The chemotherapeutic anthracycline metabolite doxorubicinol (doxOL) has been shown to interact with and disrupt the function of the cardiac ryanodine receptor Ca(2+) release channel (RyR2) in the sarcoplasmic reticulum (SR) membrane and the SR Ca(2+) binding protein calsequestrin 2 (CSQ2). Normal increases in RyR2 activity in response to increasing diastolic SR [Ca(2+)] are influenced by CSQ2 and are disrupted in arrhythmic conditions. Therefore, we explored the action of doxOL on RyR2's response to changes in luminal [Ca(2+)] seen during diastole...
November 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28912111/crispr-cas9-mediated-g4946e-substitution-in-the-ryanodine-receptor-of-spodoptera-exigua-confers-high-levels-of-resistance-to-diamide-insecticides
#19
Yayun Zuo, Hui Wang, Yanjun Xu, Jianlei Huang, Shuwen Wu, Yidong Wu, Yihua Yang
Diamide insecticides selectively activate insect ryanodine receptors (RyRs), inducing uncontrolled release of calcium ions, and causing muscle contraction, paralysis and eventually death. The RyR(G4946E) substitution associated with diamide resistance has been identified in three lepidopteran pests, Plutella xylostella, Tuta absoluta and Chilo suppressalis. Recently, the T. absoluta RyR(G4946V) mutation was knocked into the model insect Drosophila melanogaster by CRISPR/Cas9 mediated genome editing and provided in vivo functional confirmation for its role in diamide resistance...
September 12, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28899787/differential-expression-of-ryanodine-receptor-isoforms-after-spinal-cord-injury
#20
Nicolas Pelisch, Cynthia Gomes, Jacqueline M Nally, Jeffrey C Petruska, David P Stirling
Ryanodine receptors (RyRs) are highly conductive intracellular Ca(2+) release channels and are widely expressed in many tissues, including the central nervous system. RyRs have been implicated in intracellular Ca(2+) overload which can drive secondary damage following traumatic injury to the spinal cord (SCI), but the spatiotemporal expression of the three isoforms of RyRs (RyR1-3) after SCI remains unknown. Here, we analyzed the gene and protein expression of RyR isoforms in the murine lumbar dorsal root ganglion (DRG) and the spinal cord lesion site at 1, 2 and 7 d after a mild contusion SCI...
September 9, 2017: Neuroscience Letters
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