Ruhr University Bochum, Faculty of Chemistry and Biochemistry, Biochemistry II, Bochum, Germany; Ruhr University Bochum, International Graduate School for Neuroscience, Germany; University of Luebeck, Luebeck, Institute for Experimental and Clinical Pharmacology and Toxicology, Germany.
Ruhr University Bochum, International Graduate School for Neuroscience, Germany; (c)Ruhr University Bochum, Faculty of Biology and Biotechnology, Cell Morphology and Molecular Neurobiology, Germany.
Neurochem Int. 2019 Sep;128:163-174. doi: 10.1016/j.neuint.2019.04.009. Epub 2019 Apr 19.
The sodium potassium ATPase (Na/K ATPase) is essential for the maintenance of a low intracellular Na and a high intracellular K concentration. Loss of function of the Na/K ATPase due to mutations in Na/K ATPase genes, anoxic conditions, depletion of ATP or inhibition of the Na/K ATPase function using cardiac glycosides such as digitalis, causes a depolarization of the resting membrane potential. While in non-excitable cells, the uptake of glucose and amino acids is decreased if the function of the Na/K ATPase is compromised, in excitable cells the symptoms range from local hyper-excitability to inactivating depolarization. Although several studies have demonstrated the differential expression of the various Na/K ATPase alpha and beta isoforms in the brain tissue of rodents, their expression profile during development has yet to be thoroughly investigated. An immunohistochemical analysis of postnatal day 19 mouse brain showed ubiquitous expression of Na/K ATPase isoforms α1, β1 and β2 in both neurons and glial cells, whereas α2 was expressed mostly in glial cells and the α3 and β3 isoforms were expressed in neurons. Furthermore, we examined potential changes in the relative expression of the different Na/K ATPase isoforms in different brain areas of postnatal day 6 and in adult 9 months old animals using immunoblot analysis. Our results show a significant up-regulation of the α1 isoform in cortex, hippocampus and cerebellum, whereas, the α2 isoform was significantly up-regulated in midbrain. The β3 isoform showed a significant up-regulation in all brain areas investigated. The up-regulation of the α3 isoform matched that of the β2 isoform which were both significantly up-regulated in cortex, hippocampus and midbrain, suggesting that the increased maturation of the neuronal network is accompanied by an increase in expression of α3/β2 complexes in these brain structures.
钠钾三磷酸腺苷酶（Na/K ATPase）对于维持细胞内低钠离子和高钾离子浓度至关重要。由于 Na/K ATPase 基因的突变、缺氧条件、ATP 的耗竭或使用洋地黄类药物等抑制 Na/K ATPase 功能，导致 Na/K ATPase 功能丧失，会引起静息膜电位去极化。虽然在非兴奋细胞中，如果 Na/K ATPase 的功能受损，葡萄糖和氨基酸的摄取会减少，但在兴奋细胞中，症状从局部超兴奋到失活去极化不等。尽管已有多项研究表明，不同的 Na/K ATPase α 和 β 同工型在啮齿动物脑组织中有差异表达，但它们在发育过程中的表达模式尚未得到全面研究。对出生后第 19 天的小鼠大脑进行免疫组织化学分析显示，Na/K ATPase 同工型 α1、β1 和 β2 在神经元和神经胶质细胞中均广泛表达，而 α2 主要在神经胶质细胞中表达，α3 和 β3 同工型在神经元中表达。此外，我们使用免疫印迹分析检查了出生后第 6 天和成年 9 个月大的动物不同脑区不同 Na/K ATPase 同工型的相对表达的潜在变化。我们的结果表明，α1 同工型在皮质、海马和小脑中显著上调，而 α2 同工型在中脑中显著上调。β3 同工型在所有研究的脑区均表现出显著上调。α3 同工型的上调与β2 同工型的上调相匹配，α3 和β2 同工型在皮质、海马和中脑中均显著上调，这表明神经元网络的成熟增加伴随着这些脑区中α3/β2 复合物表达的增加。
