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  • Title: Mechanistic insights on KATP channel regulation from cryo-EM structures.
    Author: Driggers CM, Shyng SL.
    Journal: J Gen Physiol; 2023 Jan 02; 155(1):. PubMed ID: 36441147.
    Abstract:
    Gated by intracellular ATP and ADP, ATP-sensitive potassium (KATP) channels couple cell energetics with membrane excitability in many cell types, enabling them to control a wide range of physiological processes based on metabolic demands. The KATP channel is a complex of four potassium channel subunits from the Kir channel family, Kir6.1 or Kir6.2, and four sulfonylurea receptor subunits, SUR1, SUR2A, or SUR2B, from the ATP-binding cassette (ABC) transporter family. Dysfunction of KATP channels underlies several human diseases. The importance of these channels in human health and disease has made them attractive drug targets. How the channel subunits interact with one another and how the ligands interact with the channel to regulate channel activity have been long-standing questions in the field. In the past 5 yr, a steady stream of high-resolution KATP channel structures has been published using single-particle cryo-electron microscopy (cryo-EM). Here, we review the advances these structures bring to our understanding of channel regulation by physiological and pharmacological ligands.
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