Baruscotti Mirko, Robinson Richard B
Laboratory of Molecular Physiology and Neurobiology, Department of Biomolecular Sciences and Biotechnology, University of Milano, Milan, Italy.
Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H2613-23. doi: 10.1152/ajpheart.00750.2007. Epub 2007 Sep 7.
The sinoatrial node performs its task as a cardiac impulse generator throughout the life of the organism, but this important function is not a constant. Rather, there are significant developmental changes in the expression and function of ion channels and other cellular elements, which lead to a postnatal slowing of heart rate and may be crucial to the reliable functioning of the node during maturation. In this review, we provide an overview of current knowledge regarding these changes, with the main focus placed on maturation of the ion channel expression profile. Studies on Na(+) and pacemaker currents have shown that their contribution to automaticity is greater in the newborn than in the adult, but this age-dependent decrease is at least partially opposed by an increased contribution of L-type Ca(2+) current. Whereas information regarding age-dependent changes in other transmembrane currents within the sinoatrial node are lacking, there are data on other relevant parameters. These include an increase in the nodal content of fibroblasts and in the area of nonexpression of connexin43, considered a molecular marker of nodal tissue. Although much remains to be done before a comprehensive view of the developmental biology of the node is available, important evidence in support of a molecular interpretation of developmental slowing of the intrinsic sinoatrial rate is beginning to emerge.
窦房结在生物体的整个生命过程中作为心脏冲动发生器执行其任务,但这一重要功能并非一成不变。相反,离子通道和其他细胞成分的表达及功能存在显著的发育变化,这导致出生后心率减慢,并且可能对窦房结在成熟过程中的可靠运作至关重要。在本综述中,我们概述了关于这些变化的当前知识,主要重点放在离子通道表达谱的成熟方面。对钠电流和起搏电流的研究表明,它们对自律性的贡献在新生儿中比在成年人中更大,但这种年龄依赖性的降低至少部分地被L型钙电流贡献的增加所抵消。虽然缺乏关于窦房结内其他跨膜电流年龄依赖性变化的信息,但有关于其他相关参数的数据。这些包括成纤维细胞在窦房结中的含量增加以及连接蛋白43无表达区域的面积增加,连接蛋白43被认为是窦房结组织的分子标志物。尽管在获得关于窦房结发育生物学的全面观点之前还有很多工作要做,但支持对固有窦房率发育性减慢进行分子解释的重要证据已开始出现。