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. 2019 Feb 4;151(2):100–117. doi: 10.1085/jgp.201812138

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© 2019 Strange et al.

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

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Figure 9. — Cartoon illustrating possible mechanism of VRAC regulation by ionic strength and cell swelling-induced mechanical force. LRR region is shown in orange. Mechanical force is represented by the green springs. Conformation of the LRR region is postulated to be regulated by both cytoplasmic ionic strength and mechanical force. Under conditions of normal ionic strength (top panel), a relatively high degree of swelling is required to induce mechanical force sufficient to alter the conformation of the LRR region and trigger channel activation. Reduced cytoplasmic ionic strength (middle panel) causes a nonactivating conformational change in the LRR region. Less swelling and mechanical force is therefore required to induce further conformational changes that activate VRAC. At very low cytoplasmic ionic strength (bottom panel), conformational changes in the LRR region are sufficient to activate VRAC in the absence of cell swelling.