Chuck E T, Watanabe M
Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Dev Dyn. 1997 Jun;209(2):182-95. doi: 10.1002/(SICI)1097-0177(199706)209:2<182::AID-AJA4>3.0.CO;2-E.
Although the critical role of the His-Purkinje system (HPS) in the propagation of cardiac action potentials from the atria to the ventricular myocardium in the mature heart is well appreciated, its functional and anatomical development are not well understood. The embryonic heart begins beating early in development devoid of a mature conduction system, and the HPS cannot be identified by conventional histochemical analysis until the seventh embryonic day of chicken development. Although many biochemical markers have been found that apparently identify HPS precursors, little is known about how these biochemical markers function in the maturation of the cardiac conduction system. Using immunohistological techniques, we demonstrated that the maturation of the HPS may be observed by the expression of two distinct populations of conduction system precursors, identified by the expression of cell surface carbohydrates PSA-NCAM (PSA) and HNK-1, both of which are known to participate in cell-cell and cell-substrate interactions in the development of the nervous system. By stage 25, PSA was detected in ventricular trabeculae and the interventricular septum (IVS) in a pattern that resembles bundle branches and Purkinje fibers. Beginning at stage 28, HNK-1 epitope expression in the IVS was observed in myocardium just superior to the PSA-positive bundles in a pattern that resembles the common His bundle. This junctional region was also positive for atrial myosin heavy chain (alpha MHC), another marker for the HPS. These data suggest that a complex, coordinated process of biochemical and morphological change governs the development of the cardiac conduction system.
尽管希氏-浦肯野系统(HPS)在成熟心脏中对心脏动作电位从心房向心室心肌的传导起着关键作用已得到充分认识,但其功能和解剖学发育却尚未被完全理解。胚胎心脏在发育早期就开始跳动,此时尚无成熟的传导系统,在鸡胚胎发育的第七天之前,传统的组织化学分析无法识别出HPS。尽管已经发现了许多明显可识别HPS前体的生化标志物,但对于这些生化标志物在心脏传导系统成熟过程中如何发挥作用却知之甚少。利用免疫组织学技术,我们证明,通过两种不同群体的传导系统前体的表达可以观察到HPS的成熟,这两种前体分别通过细胞表面碳水化合物PSA-NCAM(PSA)和HNK-1的表达来识别,已知这两种碳水化合物都参与神经系统发育中的细胞-细胞和细胞-底物相互作用。到第25阶段时,在心室小梁和室间隔(IVS)中检测到PSA,其模式类似于束支和浦肯野纤维。从第28阶段开始,在IVS中观察到HNK-1表位在心肌中的表达,其位置恰好在PSA阳性束上方,模式类似于希氏束。这个连接区域对心房肌球蛋白重链(αMHC)也呈阳性,αMHC是HPS的另一个标志物。这些数据表明,生化和形态变化的复杂协调过程支配着心脏传导系统的发育。