Herrera V L, Cova T, Sassoon D, Ruiz-Opazo N
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Boston University Medical Center, Massachusetts 02118.
Am J Physiol. 1994 May;266(5 Pt 1):C1301-12. doi: 10.1152/ajpcell.1994.266.5.C1301.
Na(+)-K(+)-activated adenosine triphosphatase (Na(+)-K(+)-ATPase) is the integral membrane protein that maintains the Na(+)-K(+) electrochemical gradient across the plasma membrane. Because of the importance of the Na(+)-K(+) electrochemical gradient to fundamental and specialized cell functions, we investigated the cell-specific modulation of Na(+)-K(+)-ATPase alpha-subunit isoform (alpha 1, alpha 2, and alpha 3) gene expression in different stages of postimplantation mouse embryos and neonatal rat tissues by in situ hybridization with use of isoform-specific rat-derived antisense RNA probes. At early organogenesis (9.5-10.5 days postcoitus), we demonstrated generalized coexpression of alpha 1- and alpha 2-isoforms throughout the mouse embryo with greater levels in the developing but already functional heart, in contrast to the distinct spatially restricted alpha 3-isoform gene expression in the early developing neural tube. At midorganogenesis (15.5-16.5 days postcoitus), differential spatial variation in alpha 1-, alpha 2-, and alpha 3-isoform gene expression was already evident in all organs. Interestingly, region-specific expression patterns within single cell types were noted throughout development and were exemplified by 1) alpha 3-isoform gene expression in marginal cells of the 10.5-day-postcoitus developing neural tube; 2) alpha 1-, alpha 2-, and alpha 3-isoform gene expression in cerebellar granular cells of the 4-day-old rat brain; and 3) alpha 1- and alpha 3-isoform gene expression in 4-day-old rat ventricular cardiomyocytes. These isoform-specific changes in cellular and regional Na(+)-K(+)-ATPase alpha-isoform gene expression may play an active role in development and specialized cell functions.
钠钾激活的三磷酸腺苷酶（Na(+)-K(+)-ATP酶）是一种整合膜蛋白，它维持着跨质膜的钠钾电化学梯度。由于钠钾电化学梯度对基本细胞功能和特殊细胞功能的重要性，我们通过使用源自大鼠的亚型特异性反义RNA探针进行原位杂交，研究了植入后小鼠胚胎和新生大鼠组织不同阶段中钠钾ATP酶α亚基亚型（α1、α2和α3）基因表达的细胞特异性调控。在器官发生早期（交配后9.5 - 10.5天），我们证明α1和α2亚型在整个小鼠胚胎中普遍共表达，在发育中但已具功能的心脏中表达水平更高，与之形成对比的是，α3亚型基因在早期发育的神经管中呈现明显的空间限制性表达。在器官发生中期（交配后15.5 - 16.5天），α1、α2和α3亚型基因表达的差异空间变化在所有器官中已很明显。有趣的是，在整个发育过程中均观察到单细胞类型内的区域特异性表达模式，例如：1）交配后10.5天发育中的神经管边缘细胞中的α3亚型基因表达；2）4日龄大鼠大脑小脑颗粒细胞中的α1、α2和α3亚型基因表达；3）4日龄大鼠心室心肌细胞中的α1和α3亚型基因表达。细胞和区域钠钾ATP酶α亚型基因表达的这些亚型特异性变化可能在发育和特殊细胞功能中发挥积极作用。
