PDF(Pubmed)
Abstract：
The IgCAM coxsackie-adenovirus receptor (CAR) is essential for embryonic heart development and electrical conduction in the mature heart. However, it is not well-understood how CAR exerts these effects at the cellular level. To address this question, we analyzed the spontaneous beating of cultured embryonic hearts and cardiomyocytes from wild type and CAR knockout (KO) embryos. Surprisingly, in the absence of the CAR, cultured cardiomyocytes showed increased frequencies of beating and calcium cycling. Increased beatings of heart organ cultures were also induced by the application of reagents that bind to the extracellular region of the CAR, such as the adenovirus fiber knob. However, the calcium cycling machinery, including calcium extrusion via SERCA2 and NCX, was not disrupted in CAR KO cells. In contrast, CAR KO cardiomyocytes displayed size increases but decreased in the total numbers of membrane-localized Cx43 clusters. This was accompanied by improved cell-cell coupling between CAR KO cells, as demonstrated by increased intercellular dye diffusion. Our data indicate that the CAR may modulate the localization and oligomerization of Cx43 at the plasma membrane, which could in turn influence electrical propagation between cardiomyocytes via gap junctions.
摘要：
IgCAM柯萨奇腺病毒受体（CAR）对于胚胎心脏发育和成熟心脏的电传导至关重要。然而,目前尚不清楚CAR是如何在细胞水平上发挥这些作用的。为了解决这个问题，我们分析了来自野生型和CAR敲除(KO)胚胎的培养胚胎心脏和心肌细胞的自发跳动.令人惊讶的是,在没有汽车的情况下，培养的心肌细胞显示搏动和钙循环的频率增加。通过应用与CAR的胞外区结合的试剂也诱导了心脏器官培养物的增加的打击，如腺病毒纤维旋钮。然而,钙循环机械，包括通过SERCA2和NCX挤出钙，在CARKO细胞中没有被破坏。相比之下,CARKO心肌细胞显示大小增加,但在膜定位的Cx43簇的总数中减少。这伴随着CARKO细胞之间细胞-细胞偶联的改善，如细胞间染料扩散增加所证明的。我们的数据表明，CAR可以调节Cx43在质膜上的定位和寡聚化，这又可以通过间隙连接影响心肌细胞之间的电传播。
