Emerging role of the calcium-activated, small conductance, SK3 K+ channel in distal tubule function: regulation by TRPV4.
Emerging role of the calcium-activated, small conductance, SK3 K+ channel in distal tubule function: regulation by TRPV4.
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DOI：
10.1371/journal.pone.0095149
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
O'Neil RG
中科院分区：
文献类型：
--
作者：
Berrout J;Mamenko M;Zaika OL;Chen L;Zhang W;Pochynyuk O;O'Neil RG
Ca 2+激活的maxi-K（BK）K+通道具有低Ca 2+结合亲和力，在肾单位的远端小管中表达，并有助于流量依赖性K+分泌。在本研究中，我们证明，钙激活，SK 3（KCa2.3）K+通道，具有高钙结合亲和力，也表达在小鼠肾脏（RT-PCR，免疫印迹）。使用小管特异性标记物的免疫组织化学评价证明SK 3在远端小管和整个集合管系统中显著表达，包括连接小管（CNT）和皮质集合管（CCD）。在CNT和CCD中，K+分泌的主要位点，表达水平最高的是沿着顶端（腔）细胞膜，包括主细胞（PC）和插入细胞（IC），占据Ca 2+依赖的K+分泌通道。在天然的，分裂开放的CCD中的细胞膜电位的荧光评估表明，选择性激活的Ca 2+渗透TRPV 4通道，从而诱导Ca 2+内流和升高细胞内Ca 2+水平，激活SK 3通道和BK通道，导致细胞膜的超极化。用选择性SK拮抗剂apamin抑制SK 3通道或用选择性拮抗剂iberotoxin（IbTX）抑制BK通道，超极化反应降低到相似的程度。此外，这两种抑制剂产生了进一步的去极化，表明合作的影响，这两个通道上的Vm。可以得出结论，SK 3的功能表达在远端肾单位和集合管中，诱导TRPV 4介导的Ca 2+内流，导致细胞内Ca 2+水平升高，激活这种高Ca 2+亲和性K+通道。此外，随着表达位点定位于顶端细胞膜，特别是在CNT和CCD中，SK 3有望成为膜电位和K+分泌的Ca 2+依赖性调节的关键途径。
The Ca2+-activated, maxi-K (BK) K+ channel, with low Ca2+-binding affinity, is expressed in the distal tubule of the nephron and contributes to flow-dependent K+ secretion. In the present study we demonstrate that the Ca2+-activated, SK3 (KCa2.3) K+ channel, with high Ca2+-binding affinity, is also expressed in the mouse kidney (RT-PCR, immunoblots). Immunohistochemical evaluations using tubule specific markers demonstrate significant expression of SK3 in the distal tubule and the entire collecting duct system, including the connecting tubule (CNT) and cortical collecting duct (CCD). In CNT and CCD, main sites for K+ secretion, the highest levels of expression were along the apical (luminal) cell membranes, including for both principal cells (PCs) and intercalated cells (ICs), posturing the channel for Ca2+-dependent K+ secretion. Fluorescent assessment of cell membrane potential in native, split-opened CCD, demonstrated that selective activation of the Ca2+-permeable TRPV4 channel, thereby inducing Ca2+ influx and elevating intracellular Ca2+ levels, activated both the SK3 channel and the BK channel leading to hyperpolarization of the cell membrane. The hyperpolarization response was decreased to a similar extent by either inhibition of SK3 channel with the selective SK antagonist, apamin, or by inhibition of the BK channel with the selective antagonist, iberiotoxin (IbTX). Addition of both inhibitors produced a further depolarization, indicating cooperative effects of the two channels on Vm. It is concluded that SK3 is functionally expressed in the distal nephron and collecting ducts where induction of TRPV4-mediated Ca2+ influx, leading to elevated intracellular Ca2+ levels, activates this high Ca2+-affinity K+ channel. Further, with sites of expression localized to the apical cell membrane, especially in the CNT and CCD, SK3 is poised to be a key pathway for Ca2+-dependent regulation of membrane potential and K+ secretion.
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影响因子：
4.8
作者：
Berrout, Jonathan;Jin, Min;O'Neil, Roger G.
通讯作者：
O'Neil, Roger G.
影响因子：
7.3
作者：
Eichler, I;Wibawa, J;Köhler, R
通讯作者：
Köhler, R
影响因子：
4.8
作者：
Brenner, R;Jegla, TJ;Aldrich, RW
通讯作者：
Aldrich, RW
影响因子：
19.6
作者：
Bailey, M. A.;Cantone, A.;Malnic, G.
通讯作者：
Malnic, G.
DOI：
10.1152/ajpcell.2001.280.4.c836
发表时间：
2001-04-01
影响因子：
5.5
作者：
Barfod, ET;Moore, AL;Lidofsky, SD
通讯作者：
Lidofsky, SD