Acute administration of tumour necrosis factor-alpha induces spontaneous calcium release via the reactive oxygen species pathway in atrial myocytes
Acute administration of tumour necrosis factor-alpha induces spontaneous calcium release via the reactive oxygen species pathway in atrial myocytes
复制标题
急性给予肿瘤坏死因子-α 通过心房肌细胞中的活性氧途径诱导自发钙释放
作者：
Zuo Song;Li Lin-ling;Ruan Yan-fei;Jiang Le;Li Xin;Li Song-nan;Wen Song-nan;Bai Rong;Liu Nian;Du Xin;Dong Jian-zeng;Ma Chang-Sheng;Ma CS
AimsThe arrhythmogenic mechanisms of atrial fibrillation (AF) that are induced by acute inflammation, such as postoperative AF, are not well understood. We investigated the acute effects of tumour necrosis factor-α (TNF-α) that mimic acute inflammation on Ca2+handling in isolated atrial myocytes and its underlying mechanisms.Methods and resultsCytosol Ca2+handling and mitochondrial reactive oxygen species (ROS) production were studied in freshly isolated atrial myocytes of wild-type mice that were exposed to TNF-α (0.05 ng/mL) for 2 h by Ionoptix and confocal microscopy. The acute effects of TNF-α on Ca2+handling were decreased amplitudes and prolonged decay times of Ca2+transients in isolated atrial myocytes. A significant reduction in the sarcoplasmic reticulum (SR) Ca2+content was detected in TNF-α treated cells, which was associated with increased spontaneous Ca2+release events. In particular, physiological concentrations of TNF-α dramatically promoted the frequency of spontaneous Ca2+waves and Ca2+sparks, while the spark mass presented with reduced amplitudes and prolonged durations. The underlying mechanisms of pro-arrhythmic effects of TNF-α were further investigated. Acute exposure to TNF-α rapidly promoted mitochondrial ROS production that was correlated with the acute effect of TNF-α on Ca2+handling, and enhanced the oxidation of calcium/calmodulin-dependent protein kinase II (CaMKII) and the phosphorylation of RyR2. However, the performance of ROS inhibitor, DL-Dithiothreitol (DTT), reversed Ca2+handling disorders induced by TNF-α.ConclusionTumour necrosis factor-α rapidly increases spontaneous Ca2+release and promotes atrial arrhythmogenesis via the ROS pathway, which suggests that antioxidant therapy is a promising strategy for acute inflammation related AF.
