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.
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.
© 2022 Published by Elsevier on behalf of the American College of Cardiology Foundation.