ArticlePloS one2018
Mitochondrial Ca2+ flux modulates spontaneous electrical activity in ventricular cardiomyocytes.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Oxidative Stress, Mitochondrial Homeostasis, and Sirtuins in Atrial Fibrillation.International journal of molecular sciences · 2025Review
- Lysosomal CaCirculation. Arrhythmia and electrophysiology · 2025Article
- Lysosomal CaPNAS nexus · 2023Article
- miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure.Heart rhythm · 2023Article
- Parkin Insufficiency Accentuates High-Fat Diet-Induced Cardiac Remodeling and Contractile Dysfunction Through VDAC1-Mediated Mitochondrial CaJACC. Basic to translational science · 2022Article
- Mitochondrial CaInternational journal of molecular sciences · 2022Review
- Physiological and Pathophysiological Roles of Mitochondrial NaBiomolecules · 2021Review
- Sarcoplasmic reticulum-mitochondria communication; implications for cardiac arrhythmia.Journal of molecular and cellular cardiology · 2021Review
- CaCell calcium · 2020Review
- FUNDC1 interacts with FBXL2 to govern mitochondrial integrity and cardiac function through an IP3R3-dependent manner in obesity.Science advances · 2020Article
- IP3R-Mediated Compensatory Mechanism for Calcium Handling in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes With Cardiac Ryanodine Receptor Deficiency.Frontiers in cell and developmental biology · 2020Article
- Cytoplasmic and Mitochondrial Calcium Signaling: A Two-Way Relationship.Cold Spring Harbor perspectives in biology · 2019Review
- Mitochondrial Calcium Uniporter Structure and Function in Different Types of Muscle Tissues in Health and Disease.International journal of molecular sciences · 2019Review
- Altered Intracellular Calcium Homeostasis and Arrhythmogenesis in the Aged Heart.International journal of molecular sciences · 2019Review
- Role of mitochondrial CaArchives of biochemistry and biophysics · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionCa2+ release from sarcoplasmic reticulum (SR) is known to contribute to automaticity via the cytoplasmic Na+-Ca2+ exchanger (NCX). Mitochondria participate in Ca2+ cycling. We studied the role of mitochondrial Ca2+ flux in ventricular spontaneous electrical activity.
methodsSpontaneously contracting mouse embryonic stem cells (ESC)-derived ventricular cardiomyocytes (CMs) were differentiated from wild type and ryanodine receptor type 2 (RYR2) knockout mouse ESCs and differentiated for 19-21 days. Automaticity was also observed in human induced pluripotent stem cell (hiPSC)-derived ventricular CMs differentiated for 30 days, and acute isolated adult mouse ventricular cells in ischemic simulated buffer. Action potentials (APs) were recorded by perforated whole cell current-clamp. Cytoplasmic and mitochondrial Ca2+ transients were determined by fluorescent imaging.
resultsIn mouse ESC-derived ventricular CMs, spontaneous beating was dependent on the L-type Ca2+ channel, cytoplasmic NCX and mitochondrial NCX. Spontaneous beating was modulated by SR Ca2+ release from RYR2 or inositol trisphosphate receptors (IP3R), the pacemaker current (If) and mitochondrial Ca2+ uptake by the mitochondrial Ca2+ uniporter (MCU). In RYR2 knockout mouse ESC-derived ventricular CMs, mitochondrial Ca2+ flux influenced spontaneous beating independently of the SR Ca2+ release from RYR2, and the mitochondrial effect was dependent on IP3R SR Ca2+ release. Depolarization of mitochondria and preservation of ATP could terminate spontaneous beating. A contribution of mitochondrial Ca2+ flux to automaticity was confirmed in hiPSC-derived ventricular CMs and ischemic adult mouse ventricular CMs, confirming the findings across species and cell maturity levels.
conclusionsMitochondrial and sarcolemma NCX fluxes are required for ventricular automaticity. Mitochondrial Ca2+ uptake plays a modulatory role. Mitochondrial Ca2+ uptake through MCU is influenced by IP3R-dependent SR Ca2+ release.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.