Abstract 2898: Compartment-Specific Alteration of Intracellular Ca2+ -Handling in Tachycardia-Induced Atrial Remodeling Assessed by Confocal Ca2+ Imaging
Background: Tachycardia-induced atrial remodeling impairs intracellular centripetal Ca2+ wave propagation which is crucial for electro-mechanic coupling in atrial myocytes.
Methods: 10 rabbits underwent rapid atrial pacing (RAP,10 Hz, 5 days), 7 sham animals served as controls. ICa,L, myocyte fractional shortening (FS) and whole-cell (WC) Ca2+ transients were recorded in atrial myocytes. Sarcoplasmic reticulum (SR) Ca2+ load was assessed by caffeine-induced Ca2+ transients. Subsarcolemmal (SS) and central-cellular (CC) Ca2+ trasients were measured using confocal microscopy. Total and phosphorylation levels of Ca2+-handling and myofilament proteins were quantified in whole atria by Western blot.
Results: ICa,L and FS were reduced by 63% and 68% in RAP cells. WC Ca2+ transient amplitude was 52% lower in RAP, but SR Ca2+ load was unchanged (Table 1⇓). Caffeine-induced Ca2+ -transient decay was 59% faster in RAP cells. The intracellular centripetal Ca2+ wave was impaired in RAP cells (reduced CC/SS Ca2+ transient ratio). WC and SS Ca2+-transient decays, but not CC Ca2+-transient decay, were faster in RAP indicating NCX upregulation. Serca2a protein levels were 32% lower in RAP (Table 2⇓), other total and phosphorylation levels of Ca2+ -handling and myofilament proteins were unchanged.
Conclusion: Tachycardia-induced atrial remodeling differentially affects Ca2+ handling in the SS and CC compartment of atrial myocytes. CC Ca2+ transient amplitude was blunted compared to SS transient amplitude despite unchanged global and compartmental Ca2+ load. Faster WC and SS Ca2+ transient decays indicate increased Ca2+ extrusion by the Na+/Ca2+ exchanger in the SS compartment.