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Investigating Calcium Signaling and Its Role in Cardiac Function and Apoptosis

This study explores the intricate roles of calcium (Ca²+) signaling mechanisms in cardiac function, specifically through RyR2 and IP3 receptors. We focus on their impact on excitation-secretion coupling, contractility, and the pathological implications in conditions like chronic heart failure (CHF). The experiments utilize Jurkat T cells to analyze the activation of IP3-gated Ca²+ channels and delve into how disturbances in these pathways can lead to cell death, survival, and apoptosis through various signaling cascades. Understanding these dynamics can provide insights into potential therapeutic targets.

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Investigating Calcium Signaling and Its Role in Cardiac Function and Apoptosis

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  1. RyR2 open probability Iso CHF ECC gain Ca transient contractility [Ca] DADs - SCD Cytosolic [Ca] Time

  2. Excitation-secretion coupling Inositol 1,4,5-trisphosphate receptors

  3. IP3 signaling

  4. Stable transfectant Jurkat T cells do not express IP3R1 IP3R1

  5. Activation of IP3-gated Ca2+ channel by fyn

  6. Calcium signaling during apoptosis Growth Factor Plasma Membrane PIP2 Rec PLC- g Cytoplasm P IP3 14-3-3 P 2+ ER Bad Ca Bad B c l - 2 Degradation IP3R S ERCA 2+ Akt Ca + X ? Calcineurin Cytosolic T F B c l - 2 B c l - 2 B c l - 2 Bad DNA CAD Bcl-x Digestion Nuclear Caspases TF M M Cytochrome C Nucleus Cytoskeletal Breakdown Survival Survival Cell Death

  7. NCE mM [Ca] mitochondria nAChR CNG VDAC Stretch receptor Endoplasmic reticulum mM [Ca] PMCA IP3R SERCA 100 nM [Ca] T-tubule mM [Ca] Sarcoplasmic reticulum VGCC RyR SERCA

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