Juhaszova M, Blaustein M P
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA.
Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1800-5. doi: 10.1073/pnas.94.5.1800.
Three isoforms (alpha1, alpha2, and alpha3) of the catalytic (alpha) subunit of the plasma membrane (PM) Na+ pump have been identified in the tissues of birds and mammals. These isoforms differ in their affinities for ions and for the Na+ pump inhibitor, ouabain. In the rat, alpha1 has an unusually low affinity for ouabain. The PM of most rat cells contains both low (alpha1) and high (alpha2 or alpha3) ouabain affinity isoforms, but precise localization of specific isoforms, and their functional significance, are unknown. We employed high resolution immunocytochemical techniques to localize alpha subunit isoforms in primary cultured rat astrocytes, neurons, and arterial myocytes. Isoform alpha1 was ubiquitously distributed over the surfaces of these cells. In contrast, high ouabain affinity isoforms (alpha2 in astrocytes, alpha3 in neurons and myocytes) were confined to a reticular distribution within the PM that paralleled underlying endoplasmic or sarcoplasmic reticulum. This distribution is identical to that of the PM Na/Ca exchanger. This raises the possibility that alpha1 may regulate bulk cytosolic Na+, whereas alpha2 and alpha3 may regulate Na+ and, indirectly, Ca2+ in a restricted cytosolic space between the PM and reticulum. The high ouabain affinity Na+ pumps may thereby modulate reticulum Ca2+ content and Ca2+ signaling.
在鸟类和哺乳动物组织中已鉴定出质膜（PM）钠泵催化（α）亚基的三种同工型（α1、α2和α3）。这些同工型对离子和钠泵抑制剂哇巴因的亲和力不同。在大鼠中，α1对哇巴因的亲和力异常低。大多数大鼠细胞的质膜含有低亲和力（α1）和高亲和力（α2或α3）的哇巴因同工型，但特定同工型的精确定位及其功能意义尚不清楚。我们采用高分辨率免疫细胞化学技术在原代培养的大鼠星形胶质细胞、神经元和动脉肌细胞中定位α亚基同工型。同工型α1普遍分布在这些细胞的表面。相比之下，高哇巴因亲和力同工型（星形胶质细胞中的α2、神经元和肌细胞中的α3）局限于质膜内的网状分布，与下方的内质网或肌浆网平行。这种分布与质膜钠/钙交换器的分布相同。这就增加了一种可能性，即α1可能调节胞质溶胶中的总钠，而α2和α3可能在质膜和内质网之间有限的胞质空间中调节钠，并间接调节钙。高哇巴因亲和力钠泵可能由此调节内质网钙含量和钙信号传导。
