Ryanodine Receptor-Mediated Ca ²⁺ Events in Atrial Myocytes of Patients with Atrial Fibrillation

Abstract

Background: Many alterations in sarcoplasmic reticulum Ca²⁺ handling proteins in atrial myocytes have been associated with atrial fibrillation (AF) in clinical patients, whereas the functional consequences of these alterations mostly remain unclear. Methods and Results: To know whether or not ryanodine receptor (RyR)-mediated intracellular Ca²⁺ events in AF atrial myocytes are affected by protein alterations, we investigated spontaneous Ca²⁺ sparks and Ca²⁺ waves in intact and permeabilized atrial myocytes of AF patients (n_patients = 21) and normal sinus rhythm (NSR) patients (n_patients = 22) by laser scanning confocal microscopy. It was found that the frequency, amplitude and rise time of Ca²⁺ sparks were comparable between AF and NSR groups, while full width and full duration at half maximum intensity significantly increased in the AF group. Along with these changes, the frequency of small and global Ca²⁺ waves increased in AF atrial myocytes. Conclusions: Our results clearly indicated that the spatiotemporal properties but not the frequency of Ca²⁺ sparks were affected in AF atrial myocytes. In addition, the frequency of Ca²⁺ waves increased. This profile of the alterations in RyR-mediated Ca²⁺ events in AF atrial myocytes was different from previous studies. The underlying mechanisms, as well as possible reasons for this discrepancy, were discussed.