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J Physiol Volume 554, Number 2, 295-300, January 15, 2004 DOI: 10.1113/jphysiol.2003.047175
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SYMPOSIUM REVIEW

Gene targeting approach to clarification of ion channel function: studies of Kir6.x null mice

Susumu Seino1,2 and Takashi Miki1

1 Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan2 Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan

ATP-sensitive potassium (KATP) channels are present in many tissues, including pancreatic ß-cells, heart, skeletal muscle, vascular smooth muscle and brain, in which they couple the cell metabolic state to membrane potential. KATP channels are hetero-octameric proteins composed of the pore-forming subunits Kir6.x (Kir6.1 or Kir6.2) of the inwardly rectifying K+ channel family and the regulatory subunits SURx (SUR1, SUR2A or SUR2B), the receptor of the sulphonylureas widely used in treatment of type 2 diabetes mellitus. Different combinations of Kir6.x and SURx comprise KATP channels with distinct electrophysiological and pharmacological properties, but their physiological functions in the various tissues are unclear. Our studies of Kir6.2 null (knockout) and Kir6.1 null mice have shown that KATP channels are critical metabolic sensors in protection against acute metabolic stress such as hyperglycaemia, hypoglycaemia, ischaemia and hypoxia.

(Received 3 June 2003; accepted after revision 25 June 2003; first published online 25 June 2003)
Corresponding author S. Seino: Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.  Email: seino{at}med.kobe-u.ac.jp


This report was presented at The Journal of Physiology Symposium on Ion Channels: Their Structure, Function and Control, Fukuoka, Kyushu, Japan, 24 March 2003. It was commissioned by the Editorial Board and reflects the views of the author.




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