- Spatial Distribution of Calcium Sparks Determines Their Ability to Induce Afterdepolarizations in Human Atrial Myocytes.
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
PMID36777175
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.
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