A5056080945- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Cardiomyopathy and Myosin Studies
- Cardiac Arrhythmias and Treatments
- Cardiovascular Effects of Exercise
- Neuroscience and Neural Engineering
- Electrochemical Analysis and Applications
- Nitric Oxide and Endothelin Effects
- Circadian rhythm and melatonin
- Psoriasis: Treatment and Pathogenesis
- Air Quality and Health Impacts
- RNA and protein synthesis mechanisms
- Cardiac Valve Diseases and Treatments
- Cardiac Imaging and Diagnostics
- Coronary Interventions and Diagnostics
- Potassium and Related Disorders
- Endoplasmic Reticulum Stress and Disease
- Phosphodiesterase function and regulation
- Pericarditis and Cardiac Tamponade
- Takotsubo Cardiomyopathy and Associated Phenomena
- Cardiac tumors and thrombi
- Williams Syndrome Research
- Neuroscience and Neuropharmacology Research
- ECG Monitoring and Analysis
University of Manchester
2016-2025
Manchester Royal Infirmary
2012-2024
Manchester University NHS Foundation Trust
2018-2024
Health Innovation Manchester
2022
Manchester Academic Health Science Centre
2009-2021
Cardiovascular Research Center
2016
University of California San Francisco Medical Center
2014
Mount Sinai Medical Center
2014
Icahn School of Medicine at Mount Sinai
2014
University of Freiburg
2014
Diastolic waves of Ca 2+ release have been shown to activate delayed afterdepolarizations as well some cardiac arrhythmias. The aim this study was investigate whether increasing ryanodine receptor open probability alone or in the presence β-adrenergic stimulation produces diastolic from sarcoplasmic reticulum (SR). When voltage-clamped rat ventricular myocytes were exposed caffeine (0.5 1.0 mmol), seen accompany first few stimuli but never observed steady state. We attribute initial phase a...
Electrical activity in the heart exhibits 24-hour rhythmicity, and potentially fatal arrhythmias are more likely to occur at specific times of day. Here, we demonstrate that circadian clocks within brain set daily rhythms sinoatrial (SA) atrioventricular (AV) node activity, impose a time-of-day dependent susceptibility ventricular arrhythmia. Critically, balance inputs from autonomic nervous system cardiomyocyte clock SA AV nodes differ, this renders cardiac conduction sensitive decoupling...
Neuronal nitric oxide synthase (nNOS) has recently been shown to be a major regulator of cardiac contractility. In cellular system, we have previously that nNOS is regulated by the isoform 4b plasma membrane calcium/calmodulin-dependent ATPase (PMCA4b) through direct interaction mediated PDZ domain (PSD 95, Drosophilia Discs large protein and Zona occludens-1) on cognate ligand PMCA4b. It remains unknown, however, whether this physiological relevance in heart vivo.We generated 2 strains...
mutations of the ryanodine receptor (RyR) cause catecholaminergic polymorphic ventricular tachycardia (CPVT). These predispose to generation Ca waves and delayed afterdepolarizations during adrenergic stimulation. occur when either sarcoplasmic reticulum (SR) content is elevated above a threshold or decreased. Which these occurs in cardiac myocytes expressing CPVT unknown.we tested whether SR different between control how it relates β-adrenergic stimulation.ventricular from RyR2 R4496C(+/-)...
The aim of this work was to investigate whether it is possible remove arrhythmogenic Ca 2+ release from the sarcoplasmic reticulum that occurs in calcium overload without compromising normal systolic release. Exposure rat ventricular myocytes isoproterenol (1 μmol/L) resulted an increased amplitude transient and appearance waves diastolic Application tetracaine (25 50 decreased frequency or abolished This accompanied by increase transient. Cellular flux balance investigated integrating entry...
BACKGROUND: Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying endoplasmic reticulum degradation enhancing EDEM2 (endoplasmic degradation–enhancing alpha-mannosidase–like protein 2) regulation lipid homeostasis assess strategies that...
Abstract The Frank–Starling mechanism allows the amount of blood entering heart from veins to be precisely matched with pumped out arterial circulation. As fills during diastole, myocardium is stretched and oxidants are produced. Here we show that protein kinase G Iα (PKGIα) oxidant-activated stretch this form selectively phosphorylates cardiac phospholamban Ser16—a site important for diastolic relaxation. We find hearts Cys42Ser PKGIα knock-in (KI) mice, which resistant oxidation, have...
Background— Impaired sarcoplasmic reticular Ca 2+ uptake resulting from decreased reticulum -ATPase type 2a (SERCA2a) expression or activity is a characteristic of heart failure with its associated ventricular arrhythmias. Recent attempts at gene therapy these conditions explored strategies enhancing SERCA2a and the as novel approaches to management. We here explore role Pak1 in maintaining homeostasis electrophysiological stability under both normal physiological acute chronic β-adrenergic...
Key points For the heart to function as a pump, intracellular calcium concentration ([Ca 2+ ] i ) must increase during systole activate contraction and then fall, diastole, allow myofilaments relax refill with blood. The present study investigates control of diastolic [Ca in rat ventricular myocytes. We show that is increased by manoeuvres decrease sarcoplasmic reticulum function. This accompanied systolic such time‐averaged remains constant. report controlled balance between Ca entry efflux...
Key points Ca leak from the sarcoplasmic reticulum through ryanodine receptor (RyR) reduces amplitude of transient and slows its rate decay. In presence β‐adrenergic stimulation, RyR‐mediated produces a biphasic decay with fast early phase slow late phase. Two forms have been studied, Ca‐sensitising (induced by caffeine) non‐sensitising ryanodine) both induce transient. Only can be reversed traditional RyR inhibitors such as tetracaine. also waves. At low levels leak, waves occur. As is...
Background: The three-ringed polycyclic aromatic hydrocarbon (PAH) phenanthrene (Phe) has been implicated in the cardiotoxicity of petroleum-based pollution aquatic systems, where it disrupts contractile and electrical function fish heart. Phe is also found adsorbed to particulate matter gas phase air pollution, but date, no studies have investigated impact on mammalian cardiac function. Objectives: Our objectives were determine arrhythmogenic potential acute exposure define underlying...
Heterozygous missense variants of the cardiac ryanodine receptor gene (RYR2) cause catecholaminergic polymorphic ventricular tachycardia (CPVT). These RYR2 result in a gain function receptors, characterized by increased sensitivity to activation calcium that results an propensity develop waves and delayed afterdepolarizations. We have recently detected nonsense variant young patient who suffered unexplained arrest. To understand mechanism which this RYR2, p.(Arg4790Ter), leads arrhythmias,...
REVIEW article Front. Physiol., 01 October 2012Sec. Cardiac Electrophysiology Volume 3 - 2012 | https://doi.org/10.3389/fphys.2012.00373