Cantu syndrome-associated SUR2 (ABCC9) mutations in distinct structural domains result in K_ATP channel gain-of-function by differential mechanisms.

ABSTRACT: The complex disorder Cantu syndrome (CS) arises from gain-of-function mutations in either KCNJ8 or ABCC9, the genes encoding the Kir6.1 and SUR2 subunits of ATP-sensitive potassium (K_ATP) channels, respectively. Recent reports indicate that such mutations can increase channel activity by multiple molecular mechanisms. In this study, we determined the mechanism by which K_ATP function is altered by several substitutions in distinct structural domains of SUR2: D207E in the intracellular L0-linker and Y985S, G989E, M1060I, and R1154Q/R1154W in TMD2. We engineered substitutions at their equivalent positions in rat SUR2A (D207E, Y981S, G985E, M1056I, and R1150Q/R1150W) and investigated functional consequences using macroscopic rubidium (⁸⁶Rb^+</

SUBMITTER: McClenaghan C 

PROVIDER: S-EPMC5808765 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature