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

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. Mathematic...

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Detalles Bibliográficos
Autores: Tarifa, Carmen, Vallmitjana, Alexander, Jiménez-Sábado, Verónica, Marchena, Miquel, Llach, Anna, Herraiz-Martínez, Adela, Godoy-Marín, Héctor, Nolla-Colomer, Carme, Ginel, Antonino, Viñolas, Xavier, Montiel, José, Ciruela, Francisco, Echebarria, Blas, Benítez, Raul, Cinca, Juan, Hove-Madsen, Leif
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/338106
Acceso en línea:http://hdl.handle.net/10261/338106
Access Level:acceso abierto
Palabra clave:Atrial fibrillation
Human atrial myocyte
Ryanodine receptor
Sarcoplasmic reticulum
Transient inward currents
Descripción
Sumario: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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