Fig. 1.

Two types of general anesthetic sites in pLGICs. (A) Representative cartoons of GLIC, showing three of five subunits. Cocrystal structures show PFL (orange) bound to a pore site in the closed channel (Left), or to an intrasubunit site in the open channel (Right). (B) Cross-sectional views of GLIC transmembrane domains (M1 to M4) as in A. (Inset) Zoom views of the intrasubunit cavity for WT (Top, PDB ID code 3P50) and Trp-205 crystal structures (Bottom, PDB ID code 5MVN), with PFL and position 205 in balls-and-sticks, and pore-lining helix M2 in tan. Electrophysiology traces show 30 μM PFL inhibition of WT GLIC, and potentiation of Trp-205, respectively. (Scale bars, 1 μA vs. 2 min.)