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. 2016 Jun 28;7:259. doi: 10.3389/fphys.2016.00259

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Copyright © 2016 Retamal.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The above diagram presents what is proposed as a possible molecular mechanism to explain the CO-induced Cx46 inhibition. CO increases free radicals concentration (1) which in turn induces lipid peroxide production (2). Then, lipid peroxides can induce the carbonylation of extracellular cysteine (-SH) (3), increasing Cx46-Ca²⁺ sensitivity (4) and thus stabilizing the closed state of the loop gating (5).