Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Astrid Lindgren Children's Hospital, Q2-09 SE-171 76 Stockholm, Sweden.
J Am Soc Nephrol. 2012 Aug;23(8):1283-90. doi: 10.1681/ASN.2012010102. Epub 2012 Jun 28.
The ability of cells to maintain sharp ion gradients across their membranes is the foundation for the molecular transport and electrical excitability. Across animal species and cell types, Na(+),K(+)-adenosine triphosphatase (ATPase) is arguably the most powerful contributor to this phenomenon. By producing a steep concentration difference of sodium and potassium between the intracellular and extracellular milieu, Na(+),K(+)-ATPase in the tubules provides the driving force for renal sodium reabsorption. Pump activity is downregulated by natriuretic hormones, such as dopamine, and is upregulated by antinatriuretic hormones, such as angiotensin. In the past decade, studies have revealed a novel and surprising role: that Na(+),K(+)-ATPase is a transducer of signals from extracellular to intracellular compartments. The signaling function of Na(+),K(+)-ATPase is activated by ouabain, a mammalian steroid hormone, at far lower concentrations than those that inhibit pump activity. By promoting growth and inhibiting apoptosis, activation of Na(+),K(+)-ATPase exerts tissue-protective effects. Ouabain-stimulated Na(+),K(+)-ATPase signaling has recently shown clinical promise by protecting the malnourished embryonic kidney from adverse developmental programming. A deeper understanding of the tissue-protective role of Na(+),K(+)-ATPase signaling and the regulation of Na(+),K(+)-ATPase pumping activity is of fundamental importance for the understanding and treatment of kidney diseases and kidney-related hypertension.
细胞维持细胞膜上锐利离子梯度的能力是分子转运和电兴奋性的基础。在动物物种和细胞类型中，钠钾-三磷酸腺苷酶（ATPase）可以说是对这一现象贡献最大的因素。通过在细胞内和细胞外环境之间产生钠和钾的陡峭浓度差，肾小管中的 Na(+),K(+)-ATPase 为肾脏钠重吸收提供了驱动力。泵的活性受利钠激素（如多巴胺）下调，受抗利钠激素（如血管紧张素）上调。在过去的十年中，研究揭示了一个新的、令人惊讶的作用：Na(+),K(+)-ATPase 是细胞外信号向细胞内隔室传递的传感器。Na(+),K(+)-ATPase 的信号转导功能通过哇巴因（一种哺乳动物甾体激素）激活，其激活浓度远低于抑制泵活性的浓度。通过促进生长和抑制细胞凋亡，Na(+),K(+)-ATPase 的激活发挥组织保护作用。哇巴因刺激的 Na(+),K(+)-ATPase 信号转导最近在保护营养不良的胚胎肾脏免受不利的发育编程方面显示出了临床前景。深入了解 Na(+),K(+)-ATPase 信号转导的组织保护作用和 Na(+),K(+)-ATPase 泵活性的调节，对于理解和治疗肾脏疾病和与肾脏相关的高血压具有重要意义。
