Role of abnormal sarcoplasmic reticulum function in atrial fibrillation

Abstract

SummaryAtrial fibrillation (AF) is the most common cardiac arrhythmia, and is a cause of significant morbidity and mortality if left untreated. AF has been associated with profound changes in sarcoplasmic reticulum Ca 2+ homeostasis, which might contribute to both reduced contractile function and increased arrhythmogenesis in atria. Studies in human tissue samples and various animal models of AF have revealed changes in both expression levels and posttranslational modifications of key Ca 2+ handling proteins, which may contribute to arrhythmogenesis. In this review, we will focus on the molecular basis of alterations in sarcoplasmic reticulum Ca 2+ handling in AF and their potential therapeutic implications.

Impaired local regulation of ryanodine receptor type 2 by protein phosphatase 1 promotes atrial fibrillation

“…Previous studies have described the importance of enhanced RyR2dependent SR Ca 2+ release in the pathogenesis of AF. 24,25 However, the molecular mechanisms underlying enhanced RyR2 activity have remained incompletely understood and quite controversial. 1,6,7,10 Here, we demonstrated for the first time an important role for the local regulation of PP1 in modulating RyR2 activity in the atria.…”

Impaired local regulation of ryanodine receptor type-2 by protein phosphatase 1 promotes atrial fibrillation

“…24,25 However, the molecular mechanisms underlying enhanced RyR2 activity have remained incompletely understood and quite controversial. 1,6,7,10 Here, we demonstrated for the first time an important role for the local regulation of PP1 in modulating RyR2 activity in the atria.…”