Dongfang Tang, Jiahui Xu, Yinping Li, Piao Zhao, Xiangjin Kong, Haoliang Hu, Songping Liang, Cheng Tang, Zhonghua Liu
Inwardly-rectifying potassium channels (Kirs) are important drug targets, with antagonists for the Kir1.1, Kir4.1, and pancreatic Kir6.2/SUR1 channels being potential drug candidates for treating hypertension, depression, and diabetes, respectively. However, few peptide toxins acting on Kirs are identified and their interacting mechanisms remain largely elusive yet. Herein we showed that the centipede toxin SsTx-4 potently inhibited the Kir1.1, Kir4.1, and Kir6.2/SUR1 channels with nanomolar to submicromolar affinities, and intensively studied the molecular bases for toxin-channel interactions using patch-clamp analysis and site-directed mutations...
August 12, 2021: Journal of Biological Chemistry