Reciprocal regulation of expression of pore-forming K-ATP channel genes byhypoxia

The ATP-sensitive potassium (K-ATP) channel is thought to play an important role in the protection of heart and brain against tissue hypoxia. The gene tic regulation of the components of the channel by hypoxia has not been pre viously described. Here, we investigated the regulation of the two pore-for ming channel proteins, Kir6.1 and Kir6.2, in response to hypoxia in vivo an d in vitro. We find that these two structurally-related inwardly-rectifying potassium channel proteins are reciprocally regulated by hypoxia in vivo, with upregulation of Kir6.1 and down-regulation of Kir6.2, thereby resultin g in a significant change in the composition of the channel complex in resp onse to hypoxia. In vitro we describe neuronal and cardiac cell lines in wh ich Kir6.1 is up-regulated by hypoxia, demonstrating that Kir6.1 is a hypox ia-inducible gene. We conclude that the heart and brain display genetic pla sticity in response to hypoxic stress through specific genetic reprograming of cytoprotective channel genes.