Pulmonary vein sleeve cell excitation–contraction-coupling becomes dysynchronized by spontaneous calcium transients

Rietdorf, Katja; Masoud, Said; McDonald, Fraser; Sanderson, Michael J.; Bootman, Martin D.

doi:10.1042/bst20140299

Cited by 6 publications

(2 citation statements)

References 33 publications

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“…RyR2 and SERCA2a were identified in the PVs and the working myocytes, as previously reported (42,43). Their pattern of expression in PV cardiomyocytes resembled the pattern found in the atria, which explains the molecular basis of their contractile response to electrical excitation (44,45). In addition, intracellular Ca 2+ serves an important role in pacemaking in small mammals (46).…”

Section: Discussionmentioning

confidence: 60%

Expression of connexin 43, ion channels and Ca2+-handling proteins in rat pulmonary vein cardiomyocytes

Xiao

Cai

Atkinson

et al. 2016

Experimental and Therapeutic Medicine

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Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is thought to be triggered by ectopic beats, originating primarily in the myocardial sleeves surrounding the pulmonary veins (PVs). The mechanisms underlying these cardiac arrhythmias remain unclear. To investigate this, frozen sections of heart and lung tissue from adult rats without arrhythmia were obtained in different planes, stained with Masson's trichrome, and immunolabeled for connexin 43 (Cx43), caveolin-3 (Cav3), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), Nav1.5, Kir2.1, and the calcium handling proteins sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a (SERCA2a) and ryanodine receptor 2 (RyR2). Transverse sections offered the best view of the majority of the PVs in the tissue samples. Cx43 was observed to be expressed throughout the atria, excluding the sinoatrial and atrioventricular nodes, and in the myocardial sleeves of the PVs. In contrast, HCN4 was only expressed in the sinoatrial and atrioventricular nodes. The immunodensity of Cav3, Nav1.5, Kir2.1, SERCA2a and RyR2 in the PVs imaged was similar to that in atria. The results suggest that in the absence of arrhythmia, the investigated molecular properties of the ion channels of rat PV cardiomyocytes resemble those of the working myocardium. This indicates that ectopic beats originating in the myocardial sleeves of the PVs occur only under pathological conditions.

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Section: Discussionmentioning

confidence: 60%

Expression of connexin 43, ion channels and Ca2+-handling proteins in rat pulmonary vein cardiomyocytes

Xiao

Cai

Atkinson

et al. 2016

Experimental and Therapeutic Medicine

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“…During ageing, or in disease states such as atrial fibrillation (AF), remodelling of cellular components and Ca 2+ signalling can occur, resulting in deficient cardiac output [14][15][16][17][18][19][20]. Mistiming of cytosolic Ca 2+ signals, for example, alters the rhythmic contraction of cardiomyocytes by making cells refractory to incoming electrical signals [21]. Even modest changes in Ca 2+ signalling, if persistent, can gradually alter cardiomyocyte function [22].…”

Section: Introductionmentioning

confidence: 99%

Examining Cardiomyocyte Dysfunction Using Acute Chemical Induction of an Ageing Phenotype

Masoud

McDonald

Bister

et al. 2019

IJMS

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Much effort is focussed on understanding the structural and functional changes in the heart that underlie age-dependent deterioration of cardiac performance. Longitudinal studies, using aged animals, have pinpointed changes occurring to the contractile myocytes within the heart. However, whilst longitudinal studies are important, other experimental approaches are being advanced that can recapitulate the phenotypic changes seen during ageing. This study investigated the induction of an ageing cardiomyocyte phenotypic change by incubation of cells with hydroxyurea for several days ex vivo. Hydroxyurea incubation has been demonstrated to phenocopy age- and senescence-induced changes in neurons, but its utility for ageing studies with cardiac cells has not been examined. Incubation of neonatal rat ventricular myocytes with hydroxyurea for up to 7 days replicated specific aspects of cardiac ageing including reduced systolic calcium responses, increased alternans and a lesser ability of the cells to follow electrical pacing. Additional functional and structural changes were observed within the myocytes that pointed to ageing-like remodelling, including lipofuscin granule accumulation, reduced mitochondrial membrane potential, increased production of reactive oxygen species, and altered ultrastructure, such as mitochondria with disrupted cristae and disorganised myofibres. These data highlight the utility of alternative approaches for exploring cellular ageing whilst avoiding the costs and co-morbid factors that can affect longitudinal studies.

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Automatic Hotspots Detection for Intracellular Calcium Analysis in Fluorescence Microscopic Videos

Traore

Rietdorf

Al-Jawad

et al. 2017

Communications in Computer and Information Science

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Abstract. In recent years, life-cell imaging techniques and their software applications have become powerful tools to investigate complex biological mechanisms such as calcium signalling. In this paper, we propose an automated framework to detect areas inside cells that show changes in their calcium concentration i.e. the regions of interests or hotspots, based on videos taken after loading living mouse cardiomyocytes with fluorescent calcium reporter dyes. The proposed system allows an objective and efficient analysis through the following four key stages: 1) Pre-processing to enhance video quality, 2) First level segmentation to detect candidate hotspots based on adaptive thresholding on the frame level, 3) Second-level segmentation to fuse and identify the best hotspots from the entire video by proposing the concept of calcium fluorescence hit-ratio, and 4) Extraction of the changes of calcium fluorescence over time per hotspot. From the extracted signals, different measurements are calculated such as maximum peak amplitude, area under the curve, peak frequency, and inter-spike interval of calcium changes. The system was tested using calcium imaging data collected from Heart muscle cells. The paper argues that the automated proposal offers biologists a tool to speed up the processing time and mitigate the consequences of inter-intra observer variability.

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Pulmonary vein sleeve cell excitation–contraction-coupling becomes dysynchronized by spontaneous calcium transients

Cited by 6 publications

References 33 publications

Expression of connexin 43, ion channels and Ca2+-handling proteins in rat pulmonary vein cardiomyocytes

Expression of connexin 43, ion channels and Ca2+-handling proteins in rat pulmonary vein cardiomyocytes

Examining Cardiomyocyte Dysfunction Using Acute Chemical Induction of an Ageing Phenotype

Automatic Hotspots Detection for Intracellular Calcium Analysis in Fluorescence Microscopic Videos

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