Background: Abnormal intracellular Ca2+ homeostasis occurs in chronic atrial fibrillation(AF). The intracellular Ca2+ concentration is regulated by ryanodine and inositol 1,4,5-trisphosphate (IP3) receptors. Changes occur in ryanodine receptors in atrial tissue from patients in chronic AF. Whether AF patients have alterations in atrial IP3 receptors was investigated.
Methods: IP3 receptor expression was analyzed in the right atrial myocardium from 13 mitral valvular disease (MVD) patients with AF (MVD/AF), 5MVD patients with normal sinus rhythm(MVD/NSR), and 8 control patients with NSR(tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained preoperatively, and an immunohistochemical study was performed on the atrial tissue.
Results: The relative expression level of IP3 receptor protein was significantly greater in MVD/AF (0.75 +/- 0.26) than in MVD/NSR (0.42 +/- 0.13, p < 0.01), and both were significantly above the control value (0.14 +/- 0.08). The relative expression level of IP3 receptor mRNA was significantly greater in MVD/AF(0.028 +/- 0.008) than in control subjects (0.015 +/- 0.004, p < 0.01), but MVD/AF patients did not differ from MVD/NSR (0.020 +/- 0.006) patients. The relative expression levels of IP3 receptor protein and mRNA were higher in patients with left atrial dimension > or = 40 mm, pulmonary capillary wedge pressure > or = 10 mmHg, and right atrial pressure > or = 5 mmHg. IP3 receptors were overexpressed in the cytosol and at the nuclear envelope of atrial myocytes in MVD.
Conclusions: Since chronic mechanical overload of the atrial myocardium increases IP3 receptor expression, especially in patients with chronic AF, up-regulation of IP3 receptors may be important in modulating intracellular Ca2+ homeostasis and initiating and/or perpetuating AF.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Channels, Transporters, and Receptors at Membrane Contact Sites.
Contact (Thousand Oaks)
December 2024
Department of Physiology and Membrane Biology, University of California, Davis, CA, USA.
Membrane contact sites (MCSs) are specialized regions where two or more organelle membranes come into close apposition, typically separated by only 10-30 nm, while remaining distinct and unfused. These sites play crucial roles in cellular homeostasis, signaling, and metabolism. This review focuses on ion channels, transporters, and receptors localized to MCSs, with particular emphasis on those associated with the plasma membrane and endoplasmic reticulum (ER).
View Article and Find Full Text PDFPersonalization of a computational systems biology model of blood platelet calcium signaling.
Biomed Khim
December 2024
Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Anuclear blood cells, platelets, are the basis for the formation of blood clots in human vessels. While antiplatelet therapy is most often used after ischemic events, there is a need for its personalization due to the limited effectiveness and risks of bleeding. Previously, we developed a series of computational models to describe intracellular platelet signaling and a set of experimental methods to characterize the platelets of a given patient.
View Article and Find Full Text PDFTranscriptional regulation in the absence of inositol trisphosphate receptor calcium signaling.
Front Cell Dev Biol
December 2024
MitoCare Center, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, United States.
The activation of IP receptor (IPR) Ca channels generates agonist-mediated Ca signals that are critical for the regulation of a wide range of biological processes. It is therefore surprising that CRISPR induced loss of all three IPR isoforms (TKO) in HEK293 and HeLa cell lines yields cells that can survive, grow and divide, albeit more slowly than wild-type cells. In an effort to understand the adaptive mechanisms involved, we have examined the activity of key Ca dependent transcription factors (NFAT, CREB and AP-1) and signaling pathways using luciferase-reporter assays, phosphoprotein immunoblots and whole genome transcriptomic studies.
View Article and Find Full Text PDFPTH1R Suppressed Apoptosis of Mesenchymal Progenitors in Mandibular Growth.
Int J Mol Sci
November 2024
Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
Genetic abnormalities of the parathyroid hormone 1 receptor (PTH1R) lead to profound craniomaxillofacial bone and dentition defects on account of inappropriate tissue metabolism and cellular differentiation. The coordinated activity of differentiation and viability in bone cells is indispensable for bone metabolism. Recent research demonstrates mesenchymal progenitors are responsive to PTH1R signaling for osteogenic differentiation, whereas the effect of PTH1R on cellular survival remains incompletely understood.
View Article and Find Full Text PDFA spatial threshold for astrocyte calcium surge.
Elife
December 2024
Department of Neuroscience, University of Minnesota, Minneapolis, United States.
Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, in which astrocyte calcium plays a crucial role. Synaptically evoked calcium increases can be localized to independent subcellular domains or expand to the entire cell, i.e.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!