Two inwardly rectifying potassium channels, Irk1 and Irk2, play redundant roles in Drosophila renal tubule function.
Two inwardly rectifying potassium channels, Irk1 and Irk2, play redundant roles in Drosophila renal tubule function.
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DOI：
10.1152/ajpregu.00148.2015
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发表时间：
2015-07
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通讯作者：
Yipin Wu;M. Baum;Chou-Long Huang;Aylin R. Rodan
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作者：
Yipin Wu;M. Baum;Chou-Long Huang;Aylin R. Rodan
钾离子通道在肾脏的生理活动中起着重要的作用。钡敏感的K（+）电导存在于多种昆虫马氏管（肾）的基底膜上，包括黑腹果蝇。我们发现，钡降低了离体灌流果蝇小管的管腔阳性跨上皮电位差，并减少了液体分泌和跨上皮K（+）通量。在已经研究的昆虫物种中，编码内向整流K（+）通道的多个基因的转录物在肾（马氏）小管中表达。在黑腹果蝇中，这包括Irk 1、Irk 2和Irk 3基因的转录本。这些基因产物中的每一种在肾小管功能中的作用尚不清楚。我们发现，同时敲低苍蝇小管主细胞中的Irk 1和Irk 2可降低跨上皮K（+）通量，而Irk 3敲低无累加效应，并使跨上皮K（+）通量的钡敏感性降低约50%。单独敲除三个内向整流K（+）通道中的任何一个都没有影响，同时敲除Irk 3和Irk 1或Irk 2也没有影响。Irk 1/Irk 2主细胞双敲低小管对cAMP的排钾作用保持敏感。哇巴因和Irk 1/Irk 2双敲低抑制Na（+）/K（+）-ATP酶对K（+）通量具有累加效应，75%的跨上皮K（+）转运是由于Irk 1/Irk 2或哇巴因敏感途径。总之，Irk 1和Irk 2在果蝇肾小管跨上皮细胞离子转运中起着多余的作用，并且是Na（+）/K（+）-ATP酶依赖性途径的补充。
Inwardly rectifying potassium channels play essential roles in renal physiology across phyla. Barium-sensitive K(+) conductances are found on the basolateral membrane of a variety of insect Malpighian (renal) tubules, including Drosophila melanogaster. We found that barium decreases the lumen-positive transepithelial potential difference in isolated perfused Drosophila tubules and decreases fluid secretion and transepithelial K(+) flux. In those insect species in which it has been studied, transcripts from multiple genes encoding inwardly rectifying K(+) channels are expressed in the renal (Malpighian) tubule. In Drosophila melanogaster, this includes transcripts of the Irk1, Irk2, and Irk3 genes. The role of each of these gene products in renal tubule function is unknown. We found that simultaneous knockdown of Irk1 and Irk2 in the principal cell of the fly tubule decreases transepithelial K(+) flux, with no additive effect of Irk3 knockdown, and decreases barium sensitivity of transepithelial K(+) flux by ∼50%. Knockdown of any of the three inwardly rectifying K(+) channels individually has no effect, nor does knocking down Irk3 simultaneously with Irk1 or Irk2. Irk1/Irk2 principal cell double-knockdown tubules remain sensitive to the kaliuretic effect of cAMP. Inhibition of the Na(+)/K(+)-ATPase with ouabain and Irk1/Irk2 double knockdown have additive effects on K(+) flux, and 75% of transepithelial K(+) transport is due to Irk1/Irk2 or ouabain-sensitive pathways. In conclusion, Irk1 and Irk2 play redundant roles in transepithelial ion transport in the Drosophila melanogaster renal tubule and are additive to Na(+)/K(+)-ATPase-dependent pathways.