Epithelial Na+ Channel (ENaC) Formed by One or Two Subunits Forms Functional Channels That Respond to Shear Force
Epithelial Na+ Channel (ENaC) Formed by One or Two Subunits Forms Functional Channels That Respond to Shear Force
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DOI：
10.3389/fphys.2020.00141
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发表时间：
2020-03-17
影响因子：
4
通讯作者：
Fronius, Martin
中科院分区：
文献类型：
--
作者：
Baldin, Jan-Peter;Barth, Daniel;Fronius, Martin
典型上皮钠通道（ENaC）是脊椎动物中由α、β和γ ENaC亚基形成的异源三聚体，并且属于变性蛋白/ENaC蛋白家族。来自这个家族的蛋白质在整个动物界形成机械敏感通道。经典ENaC的活性受剪切力（SF）调节，剪切力（SF）介导肾脏中的Na+吸收和动脉的血管张力。表达分析表明，非典型的ENaC，由单个或只有两个亚基，存在于某些组织中，但它是未知的，如果这些通道响应SF。α、β、γ和δ ENaC亚基在非洲爪蟾卵母细胞中单独表达或以两种亚基的组合表达。使用双电极电压钳记录评估阿米洛利敏感电流和对SF的反应。除γ ENaC外，所有同聚体通道均提供阿米洛利敏感电流，并通过直接作用于卵母细胞的流体流响应SF。含有两个亚基的通道也被SF激活。这里，与α β γ/δ β γ ENaC相比，γ ENaC亚基在与a或d共表达时的存在增强了SF应答。总的来说，我们提供的证据表明，非规范ENaC可以形成响应SF的通道。这支持了非典型ENaC作为上皮细胞、血管细胞和感觉细胞中的机械传感器的潜在功能。
Canonical epithelial sodium channels (ENaCs) are heterotrimers formed by alpha, beta, and gamma ENaC subunits in vertebrates and belong to the Degenerin/ENaC family of proteins. Proteins from this family form mechanosensitive channels throughout the animal kingdom. Activity of canonical ENaC is regulated by shear force (SF) mediating Na+ absorption in the kidney and vascular tone of arteries. Expression analysis suggests that non-canonical ENaC, formed by single or only two subunits, exist in certain tissues, but it is unknown if these channels respond to SF. alpha, beta, gamma, and delta ENaC subunits were expressed either alone or in combinations of two subunits in Xenopus oocytes. Amiloride-sensitive currents and the responses to SF were assessed using two-electrode voltage clamp recordings. With the exception of gamma ENaC, all homomeric channels provided amiloride-sensitive currents and responded to SF applied via a fluid stream directed onto the oocytes. Channels containing two subunits were also activated by SF. Here, the presence of the gamma ENaC subunit when co-expressed with a or d augmented the SF response in comparison to the alpha beta gamma/delta beta gamma ENaC. Overall, we provide evidence that non-canonical ENaC can form channels that respond to SF. This supports a potential function of non-canonical ENaC as mechanosensors in epithelial, vascular, and sensory cells.