Cellular and Molecular Mechanisms of Atrial Arrhythmogenesis in Patients With Paroxysmal Atrial Fibrillation

Study Questions:

Do sarcoplasmic reticulum (SR) calcium-release events play a role in the genesis of paroxysmal atrial fibrillation (PAF)?


Right atrial appendages were obtained at the time of open-heart surgery from 47 patients with PAF and 73 patients without a history of PAF. Membrane currents and action potentials (APs) were recorded in isolated atrial myocytes, and the expression of multiple relevant proteins was quantitated using standard techniques.


There were no differences between the patients with and without PAF in AP duration or major calcium or sodium/calcium-exchange currents. There was evidence of altered calcium handling, with increased SR calcium leak and a greater frequency of SR calcium-release events in the PAF myocytes. The PAF myocytes displayed significantly greater susceptibility to delayed afterdepolarizations (DADs). Ryanodine receptor expression also was increased in the PAF myocytes.


The authors concluded that an abnormal degree of SR calcium leak and greater susceptibility to DADs in the atrial myocytes of patients with PAF contribute to atrial arrhythmogenesis.


The findings suggest that calcium-dependent triggered activity may be a mechanism of PAF. However, the myocytes that were used in this study were from the right atrial appendage, which is rarely, if ever, a source of PAF. There is strong clinical evidence that a large proportion of episodes of PAF are triggered/and or driven by sources arising in the muscle sleeves of the pulmonary veins. Therefore, the clinical relevance of enhanced triggered activity arising in the right atrial appendage is unclear. Also unclear is whether the results apply to the pulmonary venous muscle sleeves.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Genetic Arrhythmic Conditions, Lipid Metabolism

Keywords: Ryanodine Receptor Calcium Release Channel, Atrial Appendage, Sarcoplasmic Reticulum, Myocytes, Cardiac, Calcium

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