Intracellular potassium ion fluorescent nanoprobes for functional analysis of hERG channel via bioimaging

Abstract Dysfunction of potassium ion (K+) channels are closely related to various diseases, while the current tools for studying K+ channels are indirect methods that cannot measure the flux of K+ in live cells. Herein, we prepared K+ fluorescent nanoprobes (KFK-Cat NPs) with appropriate dissociation constant (Kd) value (127 mM K+) and excellent stability, especially photostability, for intracellular K+ sensing and imaging. An easy-operating and biocompatible method for functional measurement of human ether-a-go-go-related gene (hERG) channel activity was constructed via directly monitoring the fluctuation of K+ in KFK-Cat NPs stained hERG-HEK293 cells. Further, this method was efficient for screening of hERG channel inhibitors, the results were in accordance with the traditional patch-clamp technique and the commercially available thallium ion (Tl+) fluorescent probes assay kits. The KFK-Cat NPs were also capable of K+ imaging after endocytosed by hERG-overexpressing colon cancer cells. This work, for the first time, broadens the application of K+ fluorescent probes for functional analysis of K+ channels activity under the help of confocal laser scanning microscope (CLSM). This method shows significant potentials for drug screening and provides efficient tool for deep investigation of K+ channel-related diseases, including tumor.