The surprising complexity of K-ATP channel biology and of genetic diseases COMMENT

摘要

The ATP-sensitive K+ channel (K-ATP) is formed by the association of four inwardly rectifying K+ channel (Kir6.x) pore subunits with four sulphonylurea receptor (SUR) regulatory subunits. Kir6.x or SUR mutations result in K-ATP channelopathies, which reflect the physiological roles of these channels, including but not limited to insulin secretion, cardiac protection, and blood flow regulation. In this issue of the JCI, McClenaghan et al. explored one of the channelopathies, namely Cantu syndrome (CS), which is a result of one kind of K-ATP channel mutation. Using a knockin mouse model, the authors demonstrated that gain-of-function K-ATP mutations in vascular smooth muscle resulted in cardiac remodeling. Moreover, they were able to reverse the cardiovascular phenotypes by administering the K-ATP channel blocker glibenclamide. These results exemplify how genetic mutations can have an impact on developmental trajectories, and provide a therapeutic approach to mitigate cardiac hypertrophy in cases of CS.