Atrial tachycardia (AT) downregulates L-type Ca²⁺ current (I_CaL) and causes atrial fibrillation–promoting electric remodeling. This study assessed potential underlying signal transduction. Cultured adult canine atrial cardiomyocytes were paced at 0, 1, or 3 Hz (P0, P1, P3) for up to 24 hours. Cellular tachypacing (P3) mimicked effects of in vivo AT: decreased I_CaL and transient outward current (I_to), unchanged I_CaT, I_Kr, and I_Ks, and reduced action potential duration (APD). I_CaL was unchanged in P3 at 2 and 8 hours but decreased by 55±6% at 24 hours. Tachypacing caused Ca²⁺_i accumulation in P3 cells at 2 to 8 hours, but, by 24 hours, Ca²⁺i returned to baseline. Ca_v1.2 mRNA expression was not altered at 2 hours but decreased significantly at 8 and 24 hours (32±4% and 48±4%, respectively) and protein expression was decreased (47±8%) at 24 hours only. Suppressing Ca²⁺_i increases during tachypacing with the I_CaL blocker nimodipine or the Ca²⁺ chelator BAPTA-AM prevented I_CaL downregulation. Calcineurin activity increased in P3 at 2 and 8 hours, respectively, returning to baseline at 24 hours. Nuclear factor of activated T cells (NFAT) nuclear translocation was enhanced in P3 cells. Ca²⁺-dependent signaling was probed with inhibitors of Ca²⁺/calmodulin (W-7), calcineurin (FK-506), and NFAT (INCA6): each prevented I_CaL downregulation. Significant APD reductions (≈30%) at 24 hours in P3 cells were prevented by nimodipine, BAPTA-AM, W-7, or FK-506. Thus, rapid atrial cardiomyocyte activation causes Ca²⁺ loading, which activates the Ca²⁺-dependent calmodulin–calcineurin–NFAT system to cause transcriptional downregulation of I_CaL, restoring Ca²⁺i to normal at the cost of APD reduction. These studies elucidate for the first time the molecular feedback mechanisms underlying arrhythmogenic AT remodeling.