Knockdown of V-ATPase subunit A (atp6v1a) impairs acid secretion and ion balance in zebrafish (Danio rerio)
Knockdown of V-ATPase subunit A (atp6v1a) impairs acid secretion and ion balance in zebrafish (Danio rerio)
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DOI：
10.1152/ajpregu.00578.2006
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发表时间：
2007-05-01
影响因子：
2.8
通讯作者：
Hwang, Pung-Pung
中科院分区：
文献类型：
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作者：
Horng, Jiun-Lin;Lin, Li-Yih;Hwang, Pung-Pung
在斑马鱼胚胎皮肤中，液泡型H（+）-ATP酶（V-ATP酶，H（+）泵）主要分布在富H（+）泵细胞的顶膜上，其功能类似于哺乳动物肾脏中的泌酸闰细胞，将内源酸泵出胚胎。除了排酸外，淡水鱼鳃顶膜上的H（+）-ATP酶的产电H（+）流出被认为是Na（+）通过顶端Na（+）通道进入的驱动力。然而，该模型在体内的分子生理学证据仍然缺乏.在本研究中，我们使用吗啉修饰的反义寡核苷酸敲除H（+）-ATP酶亚基A（atp 6v 1a）的基因产物，并检查突变体的表型。H（+）-ATP酶基因敲除的胚胎表现出几种异常，包括皮肤酸分泌抑制、生长迟缓、躯干变形和内部Ca（2+）和Na（+）丢失。这一发现揭示了H（+）-ATPase在胚胎泌酸和离子平衡中的重要作用.
In the skin of zebrafish embryo, the vacuolar H(+)-ATPase (V-ATPase, H(+) pump) distributed mainly in the apical membrane of H(+)-pump-rich cells, which pump internal acid out of the embryo and function similarly to acid-secreting intercalated cells in mammalian kidney. In addition to acid excretion, the electrogenic H(+) efflux via the H(+)-ATPases in the gill apical membrane of freshwater fish was proposed to act as a driving force for Na(+) entry through the apical Na(+) channels. How- ever, convincing molecular physiological evidence in vivo for this model is still lacking. In this study, we used morpholino-modified antisense oligonucleotides to knockdown the gene product of H(+)-ATPase subunit A (atp6v1a) and examined the phenotype of the mutants. The H(+)-ATPase knockdown embryos revealed several abnormalities, including suppression of acid-secretion from skin, growth retardation, trunk deformation, and loss of internal Ca(2+) and Na(+). This finding reveals the critical role of H(+)-ATPase in embryonic acid -secretion and ion balance, as well.