Chronic catestatin treatment reduces atrial fibrillation susceptibility via improving calcium handling in post-infarction heart failure rats.

BACKGROUND: Abnormal Ca2+ handling is a pivotal element of atrial fibrillation (AF) substrates. Catestatin (CST) modulates intracellular Ca2+ handling in cardiomyocytes (CMs). We investigated the effects of CST administration on atrial Ca2+ handling and AF susceptibility in rats with post-infarction heart failure (HF). METHODS: Myocardial infarction (MI) was established by ligation of the left anterior descending coronary artery in rats. Two-week later, rats with post-infarction HF were randomly treated with saline (MI group) or CST (MI + CST group) for 4-week. Cellular Ca2+ imaging was performed by incubating atrial CMs with Fura-2 AM. An in vitro electrophysiological study was performed to assess the vulnerability to action potential duration (APD) alternans and AF. Ca2+ handling proteins expression was determined using western blotting. RESULTS: In atrial CMs, compared with the sham group, the sarcoplasmic reticulum (SR) Ca2+ load, Ca2+ transient (CaT) amplitude, and threshold for Ca2+ alternans were significantly decreased, but the diastolic intracellular Ca2+ level, SR Ca2+ leakage, and spontaneous Ca2+ events were markedly increased in the MI group. However, CST attenuated these Ca2+-handling abnormalities induced by post-infarction HF. Moreover, vulnerability to atrial APD alternans and AF was significantly increased in isolated hearts from the MI group compared to the sham group, whereas all effects were prevented by CST. CST treatment also preserved SR Ca2+-ATPase protein expression but decreased the protein levels of phosphorylated-ryanodine receptor 2 and phosphorylated-Ca2+/calmodulin-dependent protein kinase II in atria from post-infarction HF rats. CONCLUSION: Chronic CST treatment reduces AF vulnerability in rats with MI-induced HF by improving Ca2+ handling.