Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
J Physiol. 2011 Mar 15;589(Pt 6):1489-503. doi: 10.1113/jphysiol.2010.200295. Epub 2011 Jan 24.
The zebrafish, Danio rerio, is emerging as an important model organism for the pathophysiological study of some human kidney diseases, but the sites of expression and physiological roles of a number of protein orthologues in the zebrafish nephron remain mostly undefined. Here we show that a zebrafish potassium channel is orthologous to the mammalian kidney potassium channel, ROMK. The cDNA (kcnj1) encodes a protein (Kcnj1) that when expressed in Xenopus laevis oocytes displayed pH- and Ba2+-sensitive K+-selective currents, but unlike the mammalian channel, was completely insensitive to the peptide inhibitor tertiapin-Q. In the pronephros, kcnj1 transcript expression was restricted to a distal region and overlapped with that of sodium–chloride cotransporter Nkcc, chloride channel ClC-Ka, and ClC-Ka/b accessory subunit Barttin, indicating the location of the diluting segment. In a subpopulation of surface cells, kcnj1 was coexpressed with the a1a.4 isoform of the Na+/K+-ATPase, identifying these cells as potential K+ secretory cells in this epithelium. At later stages of development, kcnj1 appeared in cells of the developing gill that also expressed the a1a.4 subunit.Morpholino antisense-mediated knockdown of kcnj1 was accompanied by transient tachycardia followed by bradycardia, effects consistent with alterations in extracellular K+ concentration in the embryo.Our findings indicate that Kcnj1 is expressed in cells associated with osmoregulation and acts as a K+ efflux pathway that is important in maintaining extracellular levels of K+ in the developing embryo.
斑马鱼（Danio rerio）正在成为研究某些人类肾脏疾病病理生理学的重要模式生物，但肾脏中许多蛋白质同源物在斑马鱼肾单位中的表达部位和生理作用仍大多未定义。在这里，我们证明了一种斑马鱼钾通道与哺乳动物肾脏钾通道 ROMK 是同源的。该 cDNA（kcnj1）编码一种蛋白（Kcnj1），当在非洲爪蟾卵母细胞中表达时，显示出 pH 和 Ba2+敏感的 K+选择性电流，但与哺乳动物通道不同，它对肽抑制剂 tertiapin-Q 完全不敏感。在原肾中，kcnj1 转录本表达局限于远端区域，并与钠离子-氯化物共转运蛋白 Nkcc、氯离子通道 ClC-Ka 和 ClC-Ka/b 辅助亚基 Barttin 重叠，表明稀释段的位置。在表面细胞的亚群中，kcnj1 与 Na+/K+-ATPase 的 a1a.4 同工型共同表达，鉴定这些细胞为该上皮中潜在的 K+分泌细胞。在发育后期，kcnj1 出现在发育中的鳃中的细胞中，这些细胞也表达 a1a.4 亚基。kcnj1 的 Morpholino 反义介导的敲低伴随着短暂的心动过速，随后是心动过缓，这些效应与胚胎中外周 K+浓度的变化一致。我们的研究结果表明，Kcnj1 表达在与渗透压调节相关的细胞中，并作为 K+外排途径发挥作用，这对维持胚胎中外周 K+水平非常重要。
