Glibenclamide and HMR1098 normalize Cantu syndrome-associated gain-of-function currents.

ABSTRACT: Cantú syndrome (CS) is caused by dominant gain-of-function mutation in ATP-dependent potassium channels. Cellular ATP concentrations regulate potassium current thereby coupling energy status with membrane excitability. No specific pharmacotherapeutic options are available to treat CS but I_KATP channels are pharmaceutical targets in type II diabetes or cardiac arrhythmia treatment. We have been suggested that I_KATP inhibitors, glibenclamide and HMR1098, normalize CS channels. I_KATP in response to Mg-ATP, glibenclamide and HMR1098 were measured by inside-out patch-clamp electrophysiology. Results were interpreted in view of cryo-EM I_KATP channel structures. Mg-ATP IC₅₀ values of outward current were increased for D207E (0.71 ± 0.14 mmol/

SUBMITTER: Houtman MJC 

PROVIDER: S-EPMC7346732 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature