ENaC gating model. Two state model of heterotrimeric ENaC as viewed from the top of the channel. Each subunit is represented as an irregular trapezoid. Approximate location of α_K477 and β_V85 are indicated on the model. Cross-linking with MTS-2-MTS favors the ENaC closed state and MTS-14-O4-MTS favors the open state. ENaC gating is regulated by extracellular protons (stimulatory) and Na⁺ (inhibitory); cross-linking disrupted this regulation by preventing transitions between the open and closed states.