1. Spatial distribution of calcium sparks determines their ability to induce afterdepolarizations in human atrial myocytes
- Author
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Universitat Politècnica de Catalunya. Departament de Física, Universitat Politècnica de Catalunya. Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial, Universitat Politècnica de Catalunya. BIOCOM-SC - Biologia Computacional i Sistemes Complexos, Tarifa Lora, Carmen, Vallmitjana Lees, Alexander, Jiménez Sábado, Verónica, Marchena Angos, Miquel, Llach, Anna, Herraiz Martínez, Adela, Nolla Colomer, Carme, Ginel Iglesias, Antonino, Montiel Dacosta, José Antonio, Ciruela, Francisco, Echebarría Domínguez, Blas, Benítez Iglesias, Raúl, Cinca Cuscullola, Juan Maria, Hove-Madsen, Leif, Universitat Politècnica de Catalunya. Departament de Física, Universitat Politècnica de Catalunya. Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial, Universitat Politècnica de Catalunya. BIOCOM-SC - Biologia Computacional i Sistemes Complexos, Tarifa Lora, Carmen, Vallmitjana Lees, Alexander, Jiménez Sábado, Verónica, Marchena Angos, Miquel, Llach, Anna, Herraiz Martínez, Adela, Nolla Colomer, Carme, Ginel Iglesias, Antonino, Montiel Dacosta, José Antonio, Ciruela, Francisco, Echebarría Domínguez, Blas, Benítez Iglesias, Raúl, Cinca Cuscullola, Juan Maria, and Hove-Madsen, Leif
- Abstract
Analysis of the spatio-temporal distribution of calcium sparks showed a preferential increase in sparks near the sarcolemma in atrial myocytes from patients with atrial fibrillation (AF), linked to higher ryanodine receptor (RyR2) phosphorylation at s2808 and lower calsequestrin-2 levels. Mathematical modeling, incorporating modulation of RyR2 gating, showed that only the observed combinations of RyR2 phosphorylation and calsequestrin-2 levels can account for the spatio-temporal distribution of sparks in patients with and without AF. Furthermore, we demonstrate that preferential calcium release near the sarcolemma is key to a higher incidence and amplitude of afterdepolarizations in atrial myocytes from patients with AF., Postprint (published version)
- Published
- 2023