The renal TRPV4 channel is essential for adaptation to increased dietary potassium.
The renal TRPV4 channel is essential for adaptation to increased dietary potassium.
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DOI：
10.1016/j.kint.2016.12.010
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发表时间：
2017-06
影响因子：
19.6
通讯作者：
Pochynyuk OM
中科院分区：
文献类型：
--
作者：
Mamenko MV;Boukelmoune N;Tomilin VN;Zaika OL;Jensen VB;O'Neil RG;Pochynyuk OM
为了维持钾的动态平衡，肾脏依靠流动的钾分泌来促进尿钾，以应对饮食中钾摄入量的增加。这个过程涉及钙激活的远端肾单位即连接小管和集合管的大电导Maxi-K(BK)通道。最近的证据表明，TRPV4通道是这些肾小管中依赖血流的细胞内钙升高的关键决定因素。在这里，我们证明了增加膳食钾摄入量(5%钾)以一种醛固酮依赖的方式增加肾脏TRPV4的mRNA和蛋白水平，并导致天然集合管细胞到顶端质膜的通道重新分布。这反过来又导致在喂食高钾饮食的小鼠的新鲜分离的裂开收集管中，增强了TRPV4介导的依赖流动的钙离子反应。遗传性的TRPV4消融大大降低了集合管细胞的BK通道活性，表明钾的排泄能力降低。在TRPV4基因敲除的小鼠中，由于肾脏钾排泄不足，高钾摄入量一直导致高钾血症。因此，膳食钾对远端肾单位TRPV4活性的调节是维持全身钾平衡不可缺少的组成部分。
To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells. This, in turn, leads to augmented TRPV4-mediated flow-dependent calcium ion responses in freshly isolated split-opened collecting ducts from mice fed the high potassium diet. Genetic TRPV4 ablation greatly diminished BK channel activity in collecting duct cells pointing to a reduced capacity to excrete potassium. Consistently, elevated potassium intake induced hyperkalemia in TRPV4 knockout mice due to deficient renal potassium excretion. Thus, regulation of TRPV4 activity in the distal nephron by dietary potassium is an indispensable component of whole body potassium balance.