Zahler R, Sun W, Ardito T, Kashgarian M
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Am J Physiol. 1996 Jan;270(1 Pt 1):C361-71. doi: 10.1152/ajpcell.1996.270.1.C361.
The Na pump (Na-K-ATPase) is important for regulation of membrane potential and transport in smooth muscle and heart. The alpha (catalytic)-subunit of this pump has three isoforms: alpha 1 is ubiquitous, but alpha 2 and alpha 3 are mainly localized to excitable tissue. Physiological differences between isoforms are not completely understood, but alpha 3 pumps appear to have a lower affinity for intracellular Na and a higher ouabain affinity than alpha 1 pumps. The alpha 2-and alpha 3-isoform mRNAs are expressed at high levels in the normal adult rat cardiac conduction system. Although alpha 1 and alpha 3 are both globally expressed in neonatal rat myocardia, there is a switch in the myocardial isoform pattern from alpha 3 to alpha 2 after birth. There are also important species differences in cardiac isoform patterns. Furthermore, changes in Na-K-ATPase isoforms in heart and vascular tissue have been reported in association with hypertension, but little is known about isoform expression in normal endothelia. We therefore studied the cellular distribution of Na pump protein isoforms in neonatal and adult myocardia and endothelia. Immunohistochemical analysis of rat tissues showed that the alpha 1-isoform was expressed throughout atrial and ventricular myocardium, with alpha 1 the only isoform detectable in the adult t tubule system. Although alpha 2 was also present in ventricular myocytes, the signal was markedly stronger in conduction tissue and papillary muscle. In hearts from neonatal rats, the alpha 3-isoform predominated in the cardiac conduction system, whereas alpha 2 was not detectable in any structure except vascular endothelium. In tissues and in cell lines representing a variety of species and vessel sizes, endothelia of large vessels expressed primarily alpha 1, whereas alpha 2 could be detected in endothelia of small vessels in rat heart. No evidence of alpha 3 expression in endothelium was found. Thus the complex spatial and developmental regulation of Na pump isoform expression in cardiovascular tissues may provide additional correlates to distinct physiological roles of these transporters.
钠泵（Na-K-ATP酶）对于调节平滑肌和心脏的膜电位及物质转运很重要。该泵的α（催化）亚基有三种同工型：α1普遍存在，但α2和α3主要定位于可兴奋组织。同工型之间的生理差异尚未完全明了，但α3泵对细胞内钠的亲和力似乎低于α1泵，而对哇巴因的亲和力则高于α1泵。α2和α3同工型的mRNA在正常成年大鼠心脏传导系统中高水平表达。虽然α1和α3在新生大鼠心肌中均有整体表达，但出生后心肌同工型模式会从α3转变为α2。心脏同工型模式在不同物种间也存在重要差异。此外，已有报道称心脏和血管组织中钠钾ATP酶同工型的变化与高血压有关，但对于正常内皮细胞中的同工型表达了解甚少。因此，我们研究了钠泵蛋白同工型在新生和成年心肌及内皮细胞中的细胞分布。对大鼠组织的免疫组织化学分析表明，α1同工型在心房和心室心肌中均有表达，α1是成年横管系统中唯一可检测到的同工型。虽然α2也存在于心室肌细胞中，但在传导组织和乳头肌中的信号明显更强。在新生大鼠心脏中，α3同工型在心脏传导系统中占主导，而除血管内皮外，在任何结构中均未检测到α2。在代表各种物种和血管大小的组织及细胞系中，大血管内皮主要表达α1，而在大鼠心脏小血管内皮中可检测到α2。未发现内皮中有α3表达的证据。因此，心血管组织中钠泵同工型表达的复杂空间和发育调控可能为这些转运体的不同生理作用提供更多关联。
