Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0524, USA.
Annu Rev Physiol. 2010;72:395-412. doi: 10.1146/annurev-physiol-021909-135725.
The Na,K-ATPase is the membrane "pump" that generates the Na(+) and K(+) gradients across the plasma membrane that drives many physiological processes. This enzyme is highly sensitive to inhibition by cardiotonic steroids, most notably the digitalis/ouabain class of compounds, which have been used for centuries to treat congestive heart failure and arrhythmias. The amino acids that constitute the ouabain-binding site are highly conserved across the evolutionary spectrum. This could be fortuitous or could result from this site being conserved because it has an important biological function. New physiological approaches using genetically engineered mice are being used to define the biological significance of the "receptor function" of the Na,K-ATPase and its regulation by potential endogenous cardiotonic steroid-like compounds. These studies extend the reach of earlier studies involving the biochemical purification of endogenous regulatory ligands.
钠钾-ATP 酶是一种膜“泵”，可在质膜两侧产生钠（+）和钾（+）梯度，驱动许多生理过程。这种酶对强心甾类物质的抑制非常敏感，强心甾类物质最显著的是地高辛/哇巴因类化合物，它们已经被使用了几个世纪来治疗充血性心力衰竭和心律失常。构成哇巴因结合位点的氨基酸在进化范围内高度保守。这可能是偶然的，也可能是由于该位点受到保护，因为它具有重要的生物学功能。使用基因工程小鼠的新生理方法正在被用于定义钠钾-ATP 酶的“受体功能”及其受潜在内源性强心甾类样化合物调节的生物学意义。这些研究扩展了早期涉及内源性调节配体生化纯化的研究的范围。
