Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology.
Human cardiomyocytes express 3 distinct types of delayed rectifier potassium channels. Human ether-a-go-go-related gene (hERG) channels conduct the rapidly activating current IKr; KCNQ1/KCNE1 channels conduct the slowly activating current IKs; and Kv1.5 channels conduct an ultrarapid activating current IKur. Here the authors provide a general overview of the mechanistic and structural basis of ion selectivity, gating, and pharmacology of the 3 types of cardiac delayed rectifier potassium ion channels. Most blockers bind to S6 residues that line the central cavity of the channel, whereas activators interact with the channel at 4 symmetric binding sites outside the cavity.
Department of Medicine, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112, USA.
Wei
W
Wu
Department of Medicine, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112, USA. Electronic address: m.sanguinetti@utah.edu.
Michael C
MC
Sanguinetti
D051668:Delayed Rectifier Potassium Channels / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers
Gating; KCNA5; KCNE1; KCNQ1; Pharmacology; Potassium channel; hERG