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Spatial Distribution of Calcium Sparks Determines Their Ability to Induce Afterdepolarizations in Human Atrial Myocytes.

JACC. Basic to translational science (2023-02-14)
Carmen Tarifa, Alexander Vallmitjana, Verónica Jiménez-Sábado, Miquel Marchena, Anna Llach, Adela Herraiz-Martínez, Héctor Godoy-Marín, Carme Nolla-Colomer, Antonino Ginel, Xavier Viñolas, José Montiel, Francisco Ciruela, Blas Echebarria, Raúl Benítez, Juan Cinca, Leif Hove-Madsen
RESUMEN

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.

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Anti-Ryanodine Receptor Mouse mAb (C3-33), liquid, clone C3-33, Calbiochem®