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Introduction: Atrial fibrillation (AF) is the most common clinical arrhythmia, and contributes to cardiovascular morbidity and mortality. AF-related remodeling is mechanistically important but underlying signaling is cryptic. Nucleoplasmic Ca²⁺ regulates gene expression; the nature and significance of nuclear Ca²⁺ changes in AF is poorly understood. Here, we studied the effects of AF on atrial cardiomyocyte (ACM) nuclear Ca²⁺ and related downstream signaling.

Methods and Results: ACMs were isolated from control dogs (CTL, N=13) and dogs kept in AF for 1 week by atrial tachypacing at 600 bpm (AT-P, N=11). Immunostaining was used to detect CaMKII-delta and HDAC4 expression. Nucleoplasmic and cytoplasmic Ca²⁺ were recorded via confocal imaging in intact atrial cardiomyocytes loaded with Fluo-4 AM. [Ca²⁺]_nuc and [Ca²⁺ ]_cyto were calibrated independently by exposure of permeabilized ACMs to …