Novel gating mechanism of polyamine block in the strong inward rectifier K channel Kir2.1.
Inward rectifying K channels are essential for maintaining resting membrane potential and regulating excitability in many cell types. Previous studies have attributed the rectification properties of strong inward rectifiers such as Kir2.1 to voltage-dependent binding of intracellular polyamines or Mg to the pore (direct open channel block), thereby preventing outward passage of K ions. We have studied interactions between polyamines and the polyamine toxins philanthotoxin and argiotoxin on inward rectification in Kir2.1. We present evidence that high affinity polyamine block is not consistent with direct open channel block, but instead involves polyamines binding to another region of the channel (intrinsic gate) to form a blocking complex that occludes the pore. This interaction defines a novel mechanism of ion channel closure.
Lee
J K
JK
UCLA Cardiovascular Research Laboratory, University of California, Los Angeles, School of Medicine, Los Angeles, California 90095, USA.
John
S A
SA
Weiss
J N
JN
D000818:Animals; D015317:Biogenic Polyamines / Q000494:pharmacology*; D007210:Indoleacetic Acids / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000502:physiology; D009154:Mutation / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011073:Polyamines / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013111:Spider Venoms / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology; D014982:Xenopus laevis
D015317:Biogenic Polyamines; D007210:Indoleacetic Acids; D011073:Polyamines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D013111:Spider Venoms; D014862:Wasp Venoms; C054141:argiotoxin 659; C048056:beta-philanthotoxin