心力衰竭（HF）增加心律失常的可能性，包括心房颤动(AF),但对HF与AF的连接机制了解甚少。我们研究了来自正常心脏和衰竭心脏的兔心房肌细胞的Ca2信号传导和电生理紊乱，并确定了导致HF中房性心律失常风险较高的机制。CaT振幅中的Ca2瞬时（CaT）交替-搏动-搏动交替作为心律失常性增加的指标。我们证明，尽管动作电位持续时间没有变化，L型Ca2电流仅适度降低，但HF心房肌细胞更容易发生交替变化。Ca2/钙调蛋白依赖性激酶II（CaMKII）抑制抑制了CaT交替。内皮素-1（ET-1）和血管紧张素II（AngII）激活IP3信号导致急性，但CaT振幅和肌浆网（SR）Ca2+负荷的瞬时降低，降低了交替糖的风险。然而,长时间暴露于ET-1和AngII可增强SRCa2释放并增加交替糖的程度。抑制IP3受体可防止短暂的ET-1和AngII作用，并本身增加了CaT交替的程度。我们的数据表明，CaMKII和IP3信号的激活有助于HF的房性心律失常发生。
Heart failure (HF) increases the probability of cardiac arrhythmias, including atrial fibrillation (AF), but the mechanisms linking HF to AF are poorly understood. We investigated disturbances in Ca2+ signaling and electrophysiology in rabbit atrial myocytes from normal and failing hearts and identified mechanisms that contribute to the higher risk of atrial arrhythmias in HF. Ca2+ transient (CaT) alternans-beat-to-beat alternations in CaT amplitude-served as indicator of increased arrhythmogenicity. We demonstrate that HF atrial myocytes were more prone to alternans despite no change in action potentials duration and only moderate decrease of L-type Ca2+ current. Ca2+/calmodulin-dependent kinase II (CaMKII) inhibition suppressed CaT alternans. Activation of IP3 signaling by endothelin-1 (ET-1) and angiotensin II (Ang II) resulted in acute, but transient reduction of CaT amplitude and sarcoplasmic reticulum (SR) Ca2+ load, and lowered the alternans risk. However, prolonged exposure to ET-1 and Ang II enhanced SR Ca2+ release and increased the degree of alternans. Inhibition of IP3 receptors prevented the transient ET-1 and Ang II effects and by itself increased the degree of CaT alternans. Our data suggest that activation of CaMKII and IP3 signaling contribute to atrial arrhythmogenesis in HF.
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