Physiological and pathophysiological roles of ATP-sensitive K+ channels

ATP-sensitive potassium (KATO channels are present in many tissues, including pancreatic islet cells, heart, skeletal muscle, vascular smooth muscle, and brain, in which they couple the cell metabolic state to its membrane potential, playing a crucial role in various cellular functions. The K-ATP channel is a hetero-octamer comprising two subunits: the pore-forming subunit Kir6.x (Kir6.1 or Kir6.2) and the regulatory subunit sulfonylurea receptor SUR (SUR1 or SUR2). Kir6.x belongs to the inward rectifier K+ channel family; SUR belongs to the ATP-binding cassette protein superfamily. Heterologous expression of differing combinations of Kir6.1 or Kir6.2 and SUR1 or SUR2 variant (SUR2A or SUR2B) reconstitute different types of KATP channels with distinct electrophysiological properties and nucleotide and pharmacological sensitivities corresponding to the various KATP channels in native tissues. The physiological and pathophysiological roles of KATP channels have been studied primarily using KATP channel blockers and K+ channel openers, but there is no direct evidence on the role of the KATP channels in many important cellular responses. In addition to the analyses of naturally occurring mutations of the genes in humans, determination of the phenotypes of mice generated by genetic manipulation has been successful in clarifying the function of various gene products. Recently, various genetically engineered mice, including mice lacking KATP channels (knockout mice) and mice expressing various mutant K-ATP channels (transgenic mice), have been generated. In this review, we focus on the physiological and pathophysiological roles of KATP channels learned from genetic manipulation of mice and naturally occurring mutations in humans. (C) 2002 Elsevier Science Ltd. All rights reserved.