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.
Original language | English |
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Pages (from-to) | 1-15 |
Number of pages | 15 |
Journal | JACC: Basic to Translational Science |
Volume | 8 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2023 |
Keywords
- AF, atrial fibrillation
- Csq-2, cardiac calsequestrin (type 2)
- ICa, calcium current
- ITI, transient inward current
- NCX-1, cardiac Na+/Ca2+ exchanger (type 1)
- PLB, phospholamban
- RyR2, cardiac ryanodine receptor (type 2)
- SERCA2a, cardiac sarcoplasmic reticulum Ca-ATPase pump protein (type 2)
- SR, sarcoplasmic reticulum
- atrial fibrillation
- human atrial myocyte
- ryanodine receptor
- sarcoplasmic reticulum
- transient inward currents