A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity.
A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity.
复制标题
小鼠后左心房心肌中 Ito 和 IKACh 的区域性减少与动作电位延长和异位活动增加相关。
DOI：
10.1371/journal.pone.0154077
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kirchhof P
中科院分区：
文献类型：
--
作者：
Holmes AP;Yu TY;Tull S;Syeda F;Kuhlmann SM;O'Brien SM;Patel P;Brain KL;Pavlovic D;Brown NA;Fabritz L;Kirchhof P
左心房后壁（LAPW）可能是心房颤动发生和维持的重要区域。我们评估了整个小鼠左心房心肌是否存在区域电差异，这可能是心律失常易感性区域差异的基础。我们使用高分辨率光学测绘和清晰的微电极记录来量化完整、灌注的小鼠左心房内电激活和复极化的区域差异，并通过 Taqman 低密度阵列量化区域离子通道 mRNA 表达。我们还进行了选定的细胞电生理学实验，以验证离子通道功能的区域差异。在 10/19 完整 LA 中持续 1Hz 起搏期间观察到自发异位活动，并且在 LAPW 切除后这种现象被消除（0/19 切除 LA，P<0.001）。通过光学测绘确定，异位活动的来源是 LAPW 心肌，与肺静脉套管和 LAA 不同。总体而言，LAPW 动作电位 (AP) 约为。比 LAA 长 40%，并且该区域显示出更多的 APD 异质性。 LAPW 心肌中 Kcna4、Kcnj3 和 Kcnj5 的 mRNA 表达低于 LAA。从 LAPW 中分离出的心肌细胞在阳性和阴性测试电位下 Ito 和 IKACh 电流密度均降低。与 LA 其他区域相比，小鼠 LAPW 心肌具有不同的电表型和离子通道 mRNA 表达谱，这与异位活性增加有关。如果人类 LA 中存在类似的区域电差异，那么 LAPW 可能成为未来治疗心房颤动的潜在目标。
The left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of atrial fibrillation. We assessed whether there are regional electrical differences throughout the murine left atrial myocardium that could underlie regional differences in arrhythmia susceptibility. We used high-resolution optical mapping and sharp microelectrode recordings to quantify regional differences in electrical activation and repolarisation within the intact, superfused murine left atrium and quantified regional ion channel mRNA expression by Taqman Low Density Array. We also performed selected cellular electrophysiology experiments to validate regional differences in ion channel function. Spontaneous ectopic activity was observed during sustained 1Hz pacing in 10/19 intact LA and this was abolished following resection of LAPW (0/19 resected LA, P<0.001). The source of the ectopic activity was the LAPW myocardium, distinct from the pulmonary vein sleeve and LAA, determined by optical mapping. Overall, LAPW action potentials (APs) were ca. 40% longer than the LAA and this region displayed more APD heterogeneity. mRNA expression of Kcna4, Kcnj3 and Kcnj5 was lower in the LAPW myocardium than in the LAA. Cardiomyocytes isolated from the LAPW had decreased Ito and a reduced IKACh current density at both positive and negative test potentials. The murine LAPW myocardium has a different electrical phenotype and ion channel mRNA expression profile compared with other regions of the LA, and this is associated with increased ectopic activity. If similar regional electrical differences are present in the human LA, then the LAPW may be a potential future target for treatment of atrial fibrillation.