Surface representations of the TMDs (TMD1 and TMD2) of the ABC exporter SAV1866 (Protein Data Bank accession no. 2ONJ), viewed from the extracellular (left) or intracellular (right) side of the membrane. TMD1, TMD2, TM6, and TM12 are colored as indicated. On the same scale (black line), the blocker glibenclamide and two thiol reagents in their most extended configurations were shown for comparison. Note that the structure of the ABC protein shows an obliterated intracellular entrance, but our experimental data suggest that both glibenclamide and MTSES⁻ can readily enter the CFTR pore from the intracellular side when the channel is in the open state.