Abstract：
Cardiac conduction abnormalities are disorders in metabolic syndrome (MetS), however, their mechanisms are unknown. Although ventricular arrhythmia reflects the changes in QT-interval of electrocardiograms associated with the changes in cardiomyocyte action potential durations (APDs), recent studies emphasize role of intercellular crosstalk between cardiomyocytes and nonmyocytes via passive (electrotonic)-conduction. Therefore, considering the possible increase in intercellular interactions of nonmyocytes with cardiomyocytes, we hypothesized an early-cardiac-remodeling characterized by short QT-interval via contributions and modulations of changes by nonmyocytes to the ventricular APs in an early-stage MetS hearts. Following the feeding of 8-week-old rats with a high-sucrose diet (32%; MetS rats) and validation of insulin resistance, there was a significant increase in heart rate and changes in the electrical characteristics of the hearts, especially a shortening in action potential (AP) duration of the papillary muscles. The patch-clamp analysis of ventricular cardiomyocytes showed an increase in the Na+ -channel currents while there were decreases in l-type Ca2+ -channel (LTCC) currents with unchanged K+ -channel currents. There was an increase in the phosphorylated form of connexin 43 (pCx43), mostly with lateral localization on sarcolemma, while its unphosphorylated form (Cx43) exhibited a high degree of localization within intercalated discs. A high-level positively-stained α-SMA and CD68 cells were prominently localized and distributed in interfibrillar spaces of the heart, implying the possible contributions of myofibroblasts and macrophages to both shortened APDs and abnormal electrical conduction in MetS hearts. Our data propose a previously unrecognized pathway for SQT induction in the heart. This pathway includes not only the contribution of short ventricular-APDs via ionic mechanisms but also increasing contributions of the electrotonic-cardiomyocyte depolarization, spontaneous electrical activity-associated fast heterogeneous impulse conduction in the heart via increased interactions and relocations between cardiomyocytes and nonmyocytes, which may be an explanation for the development of an SQT in early-cardiac-remodeling.
摘要：
心脏传导异常是代谢综合征（MetS）的疾病，然而,其机制未知。尽管室性心律失常反映了与心肌细胞动作电位持续时间（APD）变化相关的心电图QT间期的变化，最近的研究强调了心肌细胞和非肌细胞之间通过被动（电渗）传导的细胞间串扰的作用。因此,考虑到非肌细胞与心肌细胞的细胞间相互作用可能增加，我们假设在早期MetS心脏中,通过非肌细胞的变化对心室AP的贡献和调节,存在以短QT间期为特征的早期心脏重构.在用高蔗糖饮食（32％;MetS大鼠）喂养8周龄大鼠并验证胰岛素抵抗后，心率显着增加，心脏的电特性发生了变化，特别是在动作电位（AP）的乳头状肌的持续时间缩短。心室心肌细胞的膜片钳分析表明，Na通道电流增加，而I型Ca2通道（LTCC）电流减少，而K通道电流不变。连接蛋白43（pCx43）的磷酸化形式增加，主要是在肌膜上横向定位，而其非磷酸化形式（Cx43）在插入的圆盘内表现出高度的定位。高水平阳性染色的α-SMA和CD68细胞明显定位并分布在心脏的纤维间隙中，暗示肌成纤维细胞和巨噬细胞对MetS心脏中缩短的APD和异常的电传导的可能贡献。我们的数据提出了以前未识别的心脏SQT诱导途径。该途径不仅包括通过离子机制的短心室APDs的贡献，还包括增加电渗心肌细胞去极化的贡献，通过增加心肌细胞和非肌细胞之间的相互作用和重新定位，在心脏中自发电活动相关的快速异质脉冲传导，这可能是早期心脏重塑中SQT发展的解释。
