Expanded gating model for TREK-2 activation. This cartoon illustrates how structurally distinct open states (e.g., O₁ and O₂) can be produced by different activatory stimuli. The model allows for the filter to gate independently in both the up and down conformations. The dotted line illustrates how the major conformational changes in the TM helices caused by, e.g., membrane stretch and temperature can also influence the filter gating mechanism. The model also shows how the channel can interconvert between different open states in response to membrane stretch.