The ATP-sensitive potassium (KATP) channel is thought to play an important role in the protection of heart and brain against tissue hypoxia. The genetic regulation of the components of the channel by hypoxia has not been previously described. Here, we investigated the regulation of the two pore-forming channel proteins, Kir6.1 and Kir6.2, in response to hypoxia in vivo and 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 resulting in a significant change in the composition of the channel complex in response to hypoxia. In vitro we describe neuronal and cardiac cell lines in which Kir6.1 is up-regulated by hypoxia, demonstrating that Kir6.1 is a hypoxia-inducible gene. We conclude that the heart and brain display genetic plasticity in response to hypoxic stress through specific genetic reprograming of cytoprotective channel genes.
Bibliographical noteFunding Information:
This work was supported by grants from the Israeli Science Foundation (APL), NIH (HL58510 to APL and HL64822 to AT) and the Bruth and Ruth Rappaport Program in Vascular Biology and Gene Delivery. AT is an E stablished Investigator of the American Heart Association.
- Gene expression
ASJC Scopus subject areas
- Molecular Biology
- Clinical Biochemistry
- Cell Biology