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上皮钾通道 Kir7.1 受孕激素刺激。

The epithelial potassium channel Kir7.1 is stimulated by progesterone.

机构信息

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA.

出版信息

J Gen Physiol. 2021 Oct 4;153(10). doi: 10.1085/jgp.202112924. Epub 2021 Aug 13.

Abstract

The choroid plexus (CP) epithelium secretes cerebrospinal fluid and plays an important role in healthy homeostasis of the brain. CP function can be influenced by sex steroid hormones; however, the precise molecular mechanism of such regulation is not well understood. Here, using whole-cell patch-clamp recordings from male and female murine CP cells, we show that application of progesterone resulted in specific and strong potentiation of the inwardly rectifying potassium channel Kir7.1, an essential protein that is expressed in CP and is required for survival. The potentiation was progesterone specific and independent of other known progesterone receptors expressed in CP. This effect was recapitulated with recombinant Kir7.1, as well as with endogenous Kir7.1 expressed in the retinal pigment epithelium. Current-clamp studies further showed a progesterone-induced hyperpolarization of CP cells. Our results provide evidence of a progesterone-driven control of tissues in which Kir7.1 is present.

摘要

脉络丛(CP)上皮分泌脑脊液,并在大脑的健康稳态中发挥重要作用。性甾体激素可以影响 CP 的功能;然而,这种调节的确切分子机制尚不清楚。在这里,我们使用来自雄性和雌性小鼠 CP 细胞的全细胞膜片钳记录,表明孕激素的应用导致了内向整流钾通道 Kir7.1 的特异性和强烈的增强,Kir7.1 是一种在 CP 中表达的必需蛋白,对于生存是必需的。这种增强作用是孕激素特异性的,与 CP 中表达的其他已知孕激素受体无关。这种作用在重组 Kir7.1 以及在视网膜色素上皮中表达的内源性 Kir7.1 中得到了重现。电流钳研究进一步表明,CP 细胞中的孕激素诱导超极化。我们的结果为存在 Kir7.1 的组织中孕激素驱动的控制提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e470/8374857/67b091278622/JGP_202112924_Fig1.jpg

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