The Emerging Structural Pharmacology of ATP-Sensitive Potassium Channels
September 2022
in “
Molecular pharmacology
”
Studysummary This article reviews current knowledge on KATP channel drug binding modes through cryogenic electron microscopy, highlighting distinct binding sites in the sulfonylurea receptor and potential mechanisms of drug action, but reports no new experimental results. Our plain-language summary of this paper — not a Tressless recommendation.
ATP-sensitive potassium channels (KATP) are crucial for energy homeostasis and are involved in various physiological processes. They are significant drug targets, with KATP inhibitors used for diabetes and KATP activators for hypoglycemia, hypertension, and hair loss. Recent cryogenic electron microscopy studies have revealed the drug binding modes, showing that inhibitors and activators bind to distinct sites in the transmembrane domain of the sulfonylurea receptor (SUR) subunit. These studies also suggest that these drugs may allosterically modulate the dimerization of SUR nucleotide-binding domains (NBDs), thereby affecting KATP channel activity.
