Abstract

ATP-sensitive potassium channels (K_ATP) are energy sensors that participate in a range of physiologic processes. These channels are also clinically validated drug targets. For decades, K_ATP inhibitors have been prescribed for diabetes and K_ATP activators have been used for the treatment of hypoglycemia, hypertension, and hair loss. In this Emerging Concepts article, we highlight our current knowledge about the drug binding modes observed using cryogenic electron microscopy techniques. The inhibitors and activators bind to two distinct sites in the transmembrane domain of the sulfonylurea receptor (SUR) subunit. We also discuss the possible mechanism of how these drugs allosterically modulate the dimerization of SUR nucleotide-binding domains (NBDs) and thus K_ATP channel activity.