Roles of ATP-Sensitive K+ Channels as Metabolic Sensors

Studies of Kir6.x Null Mice

  1. Kohtaro Minami1,
  2. Takashi Miki2,
  3. Takashi Kadowaki3 and
  4. Susumu Seino12
  1. 1Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kobe, Japan
  2. 2Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
  3. 3Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
  1. Address correspondence and reprint requests to Susumu Seino, MD, DMSc, Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. E-mail: seino{at}


ATP-sensitive K+ channels (KATP channels) are present in various tissues, including pancreatic β-cells, heart, skeletal muscles, vascular smooth muscles, and brain. KATP channels are hetero-octameric proteins composed of inwardly rectifying K+ channel (Kir6.x) and sulfonylurea receptor (SUR) subunits. Different combinations of Kir6.x and SUR subunits comprise KATP channels with distinct electrophysiological and pharmacological properties. Recent studies of genetically engineered mice have provided insight into the physiological and pathophysiological roles of Kir6.x-containing KATP channels. Analysis of Kir6.2 null mice has shown that Kir6.2/SUR1 channels in pancreatic β-cells and the hypothalamus are essential in glucose-induced insulin secretion and hypoglycemia-induced glucagon secretion, respectively, and that Kir6.2/SUR2 channels are involved in glucose uptake in skeletal muscles. Kir6.2-containing KATP channels in brain also are involved in protection from hypoxia-induced generalized seizure. In cardiovascular tissues, Kir6.1-containing KATP channels are involved in regulation of vascular tonus. In addition, the Kir6.1 null mouse is a model of Prinzmetal angina in humans. Our studies of Kir6.2 null and Kir6.1 null mice reveal that KATP channels are critical metabolic sensors in acute metabolic changes, including hyperglycemia, hypoglycemia, ischemia, and hypoxia.


  • This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.

    • Accepted May 31, 2004.
    • Received March 12, 2004.
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