Abstract 19806: Enhanced Intracellular Ca2+ Buffering Capacity Causes Failure of Intracellular Ca2+ Wave Propagation in Tachycardia-induced Atrial Remodeling
Background: Atrial tachycardia-induced remodeling leads to failure of the regenerative, centripetal intracellular Ca2+ wave propagation, which in normal atrial myocytes is an essential step of electro-mechanical coupling. Here we assessed the contribution of intracellular Ca2+ buffering capacity and transverse spacing of Ca2+ release channel (RyR2) clusters, two important determinants of centripetal intracellular Ca2+ wave propagation, to impaired Ca2+ wave propagation during rapid atrial pacing (RAP).
Methods: 7 rabbits underwent RAP (10 Hz, 5 days), 8 sham animals served as controls (CTL). Caffeine-induced (10mM) whole cell Ca2+ transients were measured in voltage-clamped myocytes to assess intracellular Ca2+ buffering capacity. Subcellular Ca2+ transients and RyR2 cluster distance (immunocytochemistry) were measured with confocal laser scanning microscopy. The fast Ca2+ chelator BAPTA-AM (1 μM) was used to assess the effect of Ca2+ buffering on Ca2+ transients. Key Ca2+ buffering proteins and RyR2 expression were quantified by immunoblotting.
Results: Treatment of CTL cells with BAPTA-AM led to failure of intracellular Ca2+ wave propagation, as in RAP, with a reduced central-cellular Ca2+ transient (2.6 ±0.3 vs 1.8 ± 0.2 ΔF/F0, respectively, p<0.05). Fast intracellular Ca2+ buffering capacity was significantly higher in RAP vs CTL cells (Fig A). Assessment of Ca2+ buffering proteins revealed a 90% increase in calmodulin expression, 30% reduction in Serca2a and no change in troponin C levels in RAP. Median RyR2 spacing was not altered (Fig B, C). RyR2 protein expression was reduced by 61%.
Conclusions: Increased fast intracellular Ca2+ buffering capacity contributes to the failure of the regenerative centripetal Ca2+ wave propagation in RAP, possibly due to increased calmodulin expression. Reduced RyR2 expression, but not alterations of RyR2 cluster spacing, might also contribute to the failure of intracellular Ca2+ wave propagation in RAP.
- © 2010 by American Heart Association, Inc.