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

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 (K) 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.