K ⁺ channels at the heart of EMS. (A) Topographic depiction of vascular K_ATP channel composition showing a two-transmembrane Kir6.1 subunit alongside its much larger companion 17-transmembrane SUR2B. (B) Side-on cryo-EM density map of the vascular K_ATP channel in the presence of the inhibitor glibenclamide. (C) Structural model of the data shown in B, showing the locations of the glibenclamide binding site (Glib), SUR nucleotide-binding domains (NBDs), ATP binding sites (ATP), and the L0 linker, as well as several transmembrane domains (TMDs). (D) Top-down view of the channel as seen from the extracellular side. (A–D) Modified with permission from Sung et al. (2021). (E) Side-on (left), top-down (upper right), and bottom-up (lower right) cryo-EM density maps of the Kir2.1 channel at 4.3 Å resolution. (F) Model of the data in E shows key structural features. K⁺ ions and blocking strontium ions (which mimic Mg²⁺ ions) are shown in the pore in magenta and green, respectively. (G) Top-down model of the channel seen from the extracellular side showing chains comprising the transmembrane domains in blue and disulfide bridges between subunits in red. (E–G) Modified with permission from Fernandes et al. (2022).