Late Sodium Current in Atrial Cardiomyocytes Contributes to the Induced and Spontaneous Atrial Fibrillation in Rabbit Hearts
Late Sodium Current in Atrial Cardiomyocytes Contributes to the Induced and Spontaneous Atrial Fibrillation in Rabbit Hearts
复制标题
心房心肌细胞中的晚钠电流导致兔心脏诱发和自发性心房颤动
DOI：
10.1097/fjc.0000000000000883
复制
发表时间：
2020-10-01
影响因子：
3
通讯作者：
Wu, Lin
中科院分区：
文献类型：
--
作者：
Chu, Yanpeng;Yang, Qiaomei;Wu, Lin
晚钠电流 (I-Na) 增加会诱发长 QT 综合征 3，并增加心房颤动 (AF) 的风险。本研究确定了心房晚期 I-Na 在诱发 AF 和治疗 AF 中的作用。在暴露于晚期 I-Na 增强剂和抑制剂的离体兔心脏中测量 AF 参数。使用全细胞膜片钳技术测量分离的心房和心室肌细胞的晚期 I-Na。我们发现，在暴露于低浓度（0.1-3 nM）或高浓度（3-10 nM）ATX-II（n = 10）的心脏中，记录了由程序化 S1S2 刺激引起的 AF 和自发的 AF 发作。复极完成 90% 时心房单相动作电位持续时间的延长以及 ATX-II (0.1-15 nM) 的有效不应期在慢速心脏中比在快速心脏中更长（n = 5-10，P < 0.05）。心房肌细胞内源性和 ATX-II 增强的晚期 I-Na 密度均大于心室肌细胞 (n = 9 和 8，P < 0.05)。 Eleclazine 和雷诺嗪可减少 AF 窗和 AF 负荷，这与抑制内源性和增强的心房晚 I-Na 相关，半数最大抑制浓度 (IC50) 分别为 1.14 和 9.78、0.94 和 8.31 muM。在心房肌细胞中，依拉嗪和雷诺嗪抑制峰值 I-Na 的 IC(50) 值分别为 20.67 和 101.79 μM。总之，心房肌细胞中晚期 I-Na 的增强会增加 AF 的易感性。抑制内源性或增强晚期 I-Na,I- 并增加药物的心房效力对于治疗 AF 是可行的。
Increased late sodium current (I-Na) induces long QT syndrome 3 with increased risk of atrial fibrillation (AF). The role of atrial late I-Na in the induction of AF and in the treatment of AF was determined in this study. AF parameters were measured in isolated rabbit hearts exposed to late I-Na enhancer and inhibitors. Late I-Na from isolated atrial and ventricular myocytes were measured using whole-cell patch-clamp techniques. We found that induced-AF by programmed S1S2 stimulation and spontaneous episodes of AF were recorded in hearts exposed to either low (0.1-3 nM) or high (3-10 nM) concentrations of ATX-II (n = 10). Prolongations in atrial monophasic action potential duration at 90% completion of repolarization and effective refractory period by ATX-II (0.1-15 nM) were greater in hearts paced at slow than at fast rates (n = 5-10, P < 0.05). Both endogenous and ATX-II-enhanced late I-Na density were greater in atrial than that in ventricular myocytes (n = 9 and 8, P < 0.05). Eleclazine and ranolazine reduced AF window and AF burden in association with the inhibition of both endogenous and enhanced atrial late I-Na with half maximal inhibitory concentrations (IC50) of 1.14 and 9.78, and 0.94 and 8.31 mu M, respectively. The IC(50)s for eleclazine and ranolazine to inhibit peak I-Na were 20.67 and 101.79 mu M, respectively, in atrial myocytes. In conclusion, enhanced late I-Na in atrial myocytes increases the susceptibility for AF. Inhibition of either endogenous or enhanced late I-Na,I- with increased atrial potency of drugs is feasible for the treatment of AF.