Abstract 3507: Functional but not Structural Changes Underlie Failure of Intracellular Calcium Wave Propagation in Tachycardia-Induced Remodeling
Background: Changes in intracellular Ca2+ handling contribute to atrial electrical and contractile remodeling induced by atrial tachyarrhythmias. In atrial myocytes, intracellular centripetal Ca2+ wave propagation is essential for electro-mechanical coupling.
Methods: 13 rabbits underwent rapid atrial pacing (RAP,10Hz) for 5 days, 13 sham operated animals served as controls. L-type Ca2+ current (ICa,L; whole cell patch clamp), myocyte fractional shortening (FS; video edge detection) and whole cell Ca2+ transients (Fura 2; field stimulation, 2Hz) were recorded in atrial myocytes. Sarcoplasmic reticulum (SR) Ca2+ load was assessed by caffeine-induced Ca2+ transients. Subsarcolemmal (ss) and central-cellular (cc) Ca2+ transients (Fluo 4) were measured by confocal laser scanning microscopy (field stimulation, 2Hz).
Results: In RAP cells, ICa,L and FS were reduced (Fig.⇓). Ca2+ transient amplitude was reduced in RAP cells while SR Ca2+ load was unchanged. In RAP cells, intracellular Ca2+ wave propagation was impaired leading to a significant reduction of the cc/ss Ca2+ transient ratio. Post-rest potentiation experiments (PRP, 20s) in RAP cells led to a recovery of the cc/ss Ca2+ transient ratio.
Conclusion: Tachycardia-induced atrial remodeling differentially affects Ca2+ handling in the subsarcolemmal and central-cellular compartment of atrial myocytes. Blunted central-cellular Ca2+ transients suggest failure of intracellular Ca2+ wave propagation in RAP cells. Recovery of the cc/ss transient ratio during post-rest potentiation points towards functional rather than structural mechanisms underlying failure of intracellular Ca2+ wave propagation.