Na+ pump low and high ouabain affinity alpha subunit isoforms are differently distributed in cells

Na+ pump low and high ouabain affinity alpha subunit isoforms are differently distributed in cells
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DOI:
10.1073/pnas.94.5.1800
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发表时间:
1997-03-04
影响因子:
11.1
通讯作者:
Blaustein, MP
Blaustein, MP
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Juhaszova, M;Blaustein, MP

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已在鸟类和哺乳动物的组织中鉴定出质膜(PM)Na+泵的催化(α)亚基的三种异构体(α 1、α 2和α 3)。这些异构体对离子和Na+泵抑制剂哇巴因的亲和力不同。在大鼠中,α 1对哇巴因的亲和力异常低。大多数大鼠细胞的PM含有低(α 1)和高(α 2或α 3)哇巴因亲和力同种型,但特定同种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对原代培养的大鼠星形胶质细胞、神经元和动脉肌细胞中的α亚基亚型进行了定位,α 1亚型广泛分布于这些细胞的表面,相反,(星形胶质细胞中的α 2,α 3)局限于PM内的网状分布,其覆盖了下面的内质网或肌浆网。这种分布与PM Na/Ca交换器的分布相同。这提出了α 1可能调节大量胞质Na+的可能性,而α 2和α 3可能调节PM和网状物之间有限的胞质空间中的Na+,并间接调节Ca 2+。高哇巴因亲和力的Na+泵可能因此调节网Ca 2+含量和Ca 2+信号传导。
Three isoforms (alpha 1, alpha 2, and alpha 3) 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, alpha 1 has an unusually low affinity for ouabain. The PM of most rat cells contains both low (alpha 1) and high (alpha 2 or alpha 3) 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 alpha 1 was ubiquitously distributed over the surfaces of these cells, In contrast, high ouabain affinity isoforms (alpha 2 in astrocytes, alpha 3 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 alpha 1 may regulate bulk cytosolic Na+, whereas alpha 2 and alpha 3 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.