Our objective was to investigate the effect of desmin depletion on the structure and function of the sinoatrial pacemaker complex, (SANcl) and their implication in arrhythmogenesis. Analysis of mice and human (SANcl) indicated that SAN exhibits high amounts of desmin, desmoplakin, N-cadherin and β-catenin in structures we call "lateral IDs", connecting myocytes side-by-side. Examination of the SANcl from an arrhythmogenic cardiomyopathy model, desmin-deficient (Des-/-) mouse, by immunofluorescence, ultrastructural and western blot analysis showed that the number of these "lateral IDs" was diminished. Also, electrophysiological recordings of isolated compact sinoatrial node (C-SAN), revealed increased pacemaker systolic potential and higher diastolic depolarization rate compared to wild-type (WT) mice. Prolonged interatrial conduction expressed as a longer P-wave duration was also observed in Des-/- mice. Upregulation of both I_CaT channels, Cav3.1 and Cav3.2 RNA levels in the Des-/- myocardium (1.8- and 2.3-fold, respectively) and a 1.9-fold reduction of the funny channel HCN1 could underlie these functional differences. To investigate arrhythmogenicity, electrocardiographic analysis of Des-deficient mice revealed a major increase in supraventricular and ventricular ectopic beats compared to WT. Heart rate variability analysis indicates a sympathetic predominance in Des-/- mice, which may further contribute to arrhythmogenicity. In conclusion, our results indicate that desmin elimination leads to structural and functional abnormalities of the (SANcl). These alterations may be enhanced by the sympathetic component of the cardiac autonomic nervous system, which is predominant in the desmin-deficient heart, thus leading to increased arrhythmogenesis.

中文翻译：

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结蛋白对于窦房结的结构和功能至关重要：对增加心律失常的影响。

我们的目的是研究结节耗竭对窦房起搏器复合体（SANcl）的结构和功能的影响及其在心律失常中的意义。对小鼠和人类（SANcl）的分析表明，SAN在我们称为“侧向ID”的结构中并排连接着心肌细胞，它们表现出大量的desmin，desmoplakin，N-cadherin和β-catenin。通过免疫荧光，超微结构和western印迹分析，从心律失常性心肌病模型，结蛋白缺乏（Des-/-）小鼠中检查SANcl，结果表明这些“侧ID”的数量减少了。同样，孤立的紧凑型窦房结（C-SAN）的电生理记录显示，与野生型（WT）小鼠相比，起搏器的收缩电位增加，舒张去极化率更高。在Des-/-小鼠中还观察到表现为P波持续时间较长的心房传导延长。我都上调了。_猫在Des-/-心肌通道中，Cav3.1和Cav3.2 RNA水平（分别为1.8和2.3倍）以及有趣通道HCN1降低1.9倍可能是这些功能差异的基础。为了研究心律失常性，对Des缺陷型小鼠的心电图分析显示，与WT相比，室上和心室异位搏动显着增加。心率变异性分析表明Des-/-小鼠具有交感神经优势，这可能进一步导致心律失常。总之，我们的结果表明，去除结蛋白会导致（SANcl）的结构和功能异常。心脏自主神经系统的交感成分可能会增强这些改变，这种交感成分主要存在于结蛋白缺乏的心脏中，从而导致心律失常的增加。