Kondapalli Kalyan C, Todd Alexander R, Pluznick Jennifer L, Rao Rajini
Department of Physiology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205, USA.
Department of Natural Sciences, University of Michigan-Dearborn, 4901 Evergreen Road, Dearborn, MI, 48128, USA.
J Physiol Biochem. 2017 May;73(2):199-205. doi: 10.1007/s13105-016-0539-8. Epub 2016 Dec 1.
Increased renal reabsorption of sodium is a significant risk factor in hypertension. An established clinical marker for essential hypertension is elevated sodium lithium countertransport (SLC) activity. NHA2 is a newly identified Na(Li)/H antiporter with potential genetic links to hypertension, which has been shown to mediate SLC activity and H-coupled Na(Li) efflux in kidney-derived MDCK cells. To evaluate a putative role in sodium homeostasis, we determined the effect of dietary salt on NHA2. In murine kidney sections, NHA2 localized apically to distal convoluted (both DCT1 and 2) and connecting tubules, partially overlapping in distribution with V-ATPase, AQP2, and NCC1 transporters. Mice fed a diet high in sodium chloride showed elevated transcripts and expression of NHA2 protein. We propose a model in which NHA2 plays a dual role in salt reabsorption or secretion, depending on the coupling ion (sodium or protons). The identified novel regulation of Na/H antiporter in the kidney suggests new roles in salt homeostasis and disease.
肾脏对钠的重吸收增加是高血压的一个重要危险因素。原发性高血压的一个既定临床标志物是钠锂逆向转运（SLC）活性升高。NHA2是一种新发现的Na(Li)/H反向转运体，与高血压存在潜在的遗传联系，已被证明可介导肾脏来源的MDCK细胞中的SLC活性和H偶联的Na(Li)流出。为了评估其在钠稳态中的假定作用，我们确定了饮食盐对NHA2的影响。在小鼠肾脏切片中，NHA2定位于远曲小管（DCT1和DCT2）和连接小管的顶端，其分布与V-ATP酶、水通道蛋白2和NCC1转运体部分重叠。喂食高氯化钠饮食的小鼠显示NHA2转录本和蛋白表达升高。我们提出了一个模型，其中NHA2在盐的重吸收或分泌中起双重作用，这取决于偶联离子（钠或质子）。在肾脏中发现的Na/H反向转运体的新调节表明其在盐稳态和疾病中具有新的作用。
