Identification and apical membrane localization of an electrogenic Na+/Ca2+ exchanger NCX2a likely to be involved in renal Ca2+ excretion by seawater fish

Identification and apical membrane localization of an electrogenic Na+/Ca2+ exchanger NCX2a likely to be involved in renal Ca2+ excretion by seawater fish
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DOI:
10.1152/ajpregu.00165.2011
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发表时间:
2011-11-01
影响因子:
2.8
通讯作者:
Hirose, Shigehisa
Hirose, Shigehisa
中科院分区:
医学3区
文献类型:
--
作者:
Islam, Zinia;Kato, Akira;Hirose, Shigehisa

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Islam Z,Kato A,Romero MF,Hirose S。可能参与海水鱼肾 Ca2+ 排泄的产电 Na+/Ca2+ 交换器 NCX2a 的鉴定和顶膜定位。 Am J Physiol Regul Integr Comp Physiol 301:R1427-R1439,2011。首次发表于 2011 年 8 月 31 日; doi:10.1152/ajpregu.00165.2011.-海水 (SW) 含有约 10 mM Ca2+,但海水鱼类必须饮用海水作为主要水源。因此海洋硬骨鱼需要排出Ca2+来维持全身Ca2+稳态。在肠道中,海水Ca2+通过肠上皮与上皮分泌的HCO3-相互作用,生成CaCO3沉淀,并经直肠排出。最近,参与肠道 HCO3- 分泌的转运蛋白被鉴定出来。 Ca2+ 也由肾脏排泄,但参与肾脏 Ca2+ 排泄的蛋白质尚未确定。在这里,我们通过使用西南河豚 torafugu (Takifugu rubripes) 及其密切相关的广盐物种 mefugu (Takifugu obscurus) 确定了一个候选转运蛋白,它们正在成为研究海水适应分子机制的有用动物模型。对各种虎河豚组织中 Na+/Ca2+ 交换器 (NCX) 家族成员的 RT-PCR 分析表明,只有 NCX2a 在肾脏中高表达。当mefugu从淡水转移到海水时,NCX2a的肾脏表达显着升高。原位杂交和免疫组织化学分析表明NCX2a在近曲小管顶膜处表达。 NCX2a 在爪蟾卵母细胞中表达,赋予 [Ca2+](out-) 和 Na+ 依赖性电流。这些结果表明NCX2a介导肾近曲小管顶膜处的肾Ca2+分泌,并且在海洋硬骨鱼全身Ca2+稳态中具有重要作用。
Islam Z, Kato A, Romero MF, Hirose S. Identification and apical membrane localization of an electrogenic Na+/Ca2+ exchanger NCX2a likely to be involved in renal Ca2+ excretion by seawater fish. Am J Physiol Regul Integr Comp Physiol 301: R1427-R1439, 2011. First published August 31, 2011; doi:10.1152/ajpregu.00165.2011.-Seawater (SW) contains similar to 10 mM Ca2+, yet marine fish must drink seawater as their major water source. Thus marine teleosts fish need to excrete Ca2+ to maintain whole body Ca2+ homeostasis. In the intestine, seawater Ca2+ interreacts with epithelial-secreted HCO3- by the intestinal epithelium, and the resulting CaCO3 precipitates, which is rectally excreted. Recently the transporters involved in intestinal HCO3- secretion were identified. Ca2+ is also excreted by the kidney, but the protein(s) involved in renal Ca2+ excretion have not been identified. Here we identified a candidate transporter by using SW pufferfish torafugu (Takifugu rubripes) and its closely related euryhaline species mefugu (Takifugu obscurus), which are becoming useful animal models for studying molecular mechanisms of seawater adaptation. RT-PCR analyses of Na+/Ca2+ exchanger (NCX) family members in various torafugu tissues demonstrated that only NCX2a is highly expressed in the kidney. Renal expression of NCX2a was markedly elevated when mefugu were transferred from freshwater to seawater. In situ hybridization and immunohistochemical analyses indicated that NCX2a is expressed in the proximal tubule at the apical membrane. NCX2a, expressed in Xenopus oocytes, conferred [Ca2+](out-) and Na+-dependent currents. These results suggest that NCX2a mediates renal Ca2+ secretion at the apical membrane of renal proximal tubules and has an important role in whole body Ca2+ homeostasis of marine teleosts.