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• W3176134414 abstract "The epithelial sodium channel (ENaC) is expressed in the kidney and vasculature and is important for blood pressure regulation. In the kidney and vasculature, ENaC is exposed to mechanical force such as shear force (SF) caused by the urine or blood flow. Canonical ENaC consists of three homologous subunits: α, β, γ and studies have shown that α-ENaC plays an important role for the ability of the channel to respond to SF. Further evidence suggests that β-and γ-ENaC alone may be involved in mechanotransduction processes in arteries. Since little is known about the function of individual ENaC subunits and their regulation by SF, this project aims to characterize the role of β- and γ-ENaC for SF sensation. Human ENaCs were expressed as homotrimers (α, β or γ alone) or heterotrimers (αβ, αγ or βγ) in Xenopus oocytes. Two-electrode voltage-clamp experiments were performed to measure ENaC activity in response to a fluid stream used for the application of SF. SF responses were normalized and expressed as percentage. Homotrimeric α-ENaC showed an activation of 46 ± 7.4 (Mean ± SEM, p < 0.0001, n = 19) in response to SF, whereas homotrimeric β- or γ-ENaCs did not respond to SF. In heterotrimeric αβ-ENaC channels the activation by SF was 17 ± 3 (p < 0.0001, n = 19) and in heterotrimeric αγ-ENaC 222 ± 35 (p < 0.0001, n = 17). Heterotrimeric βγ-ENaC did not respond to SF. Homotrimeric α-ENaC form a functional channel that responds to SF whereas β- and γ-ENaC did not. Heterotrimeric αβ-ENaC showed a lower SF responds, whereas αγ-ENaC showed a higher responds to SF. This experiments identify a modulatory role of β- and γ-ENaC for the activation in response to SF. Therefore, ENaC dysfunction is observed in hypertension may be due to changes in β- and γ-ENaC expression that could influence its activity in response to SF caused by the urine or blood flow. Support or Funding Information University of Otago Doctoral Scholarship Department of Physiology Royal Society Te Aparangi - Marsden Fund This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal." @default.
• W3176134414 created "2021-07-05" @default.
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• W3176134414 date "2018-04-01" @default.
• W3176134414 modified "2023-09-23" @default.
• W3176134414 title "The β‐ and γ Epithelial Na + Channel (ENaC) Subunits Modulate the Shear Force Activation" @default.
• W3176134414 doi "https://doi.org/10.1096/fasebj.2018.32.1_supplement.624.10" @default.
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