Potassium channels that are inhibited by internal ATP (KATP channels) provide a critical link between metabolism and cellular excitability. Protein kinase C (PKC) acts on KATP channels to regulate diverse cellular processes, including cardioprotection by ischemic preconditioning and pancreatic insulin secretion. PKC action decreases the Hill coefficient of ATP binding to cardiac KATP channels, thereby increasing their open probability at physiological ATP concentrations. We show that PKC similarly regulates recombinant channels from both the pancreas and heart. Surprisingly, PKC acts via phosphorylation of a specific, conserved threonine residue (T180) in the pore-forming subunit (Kir6.2). Additional PKC consensus sites exist on both Kir and the larger sulfonylurea receptor (SUR) subunits. Nonetheless, T180 controls changes in open probability induced by direct PKC action either in the absence of, or in complex with, the accessory SUR1 (pancreatic) or SUR2A (cardiac) subunits. The high degree of conservation of this site among different KATP channel isoforms suggests that this pathway may have wide significance for the physiological regulation of KATP channels in various tissues and organelles.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 1 Aug 2000|
Light, P. E., Bladen, C., Winkfein, R. J., Walsh, M. P., & French, R. J. (2000). Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium channels. Proceedings of the National Academy of Sciences of the United States of America, 97(16), 9058-9063. https://doi.org/10.1073/pnas.160068997