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Different types of natural K+ channels share similar core modules and cation permeability characteristics. In this study, we have developed novel artificial K+ channels by rebuilding the core modules of natural K+ channels in artificial systems. All the channels displayed high selectivity for K+ over Na+ and exhibited a selectivity sequence of K+≈Rb+ during the transport process, which is highly consistent with the cation permeability characteristics of natural K+ channels. More importantly, these artificial channels could be efficiently inserted into cell membranes and mediate the transmembrane transport of K+, disrupting the cellular K+ homeostasis and eventually triggering the apoptosis of cells. These findings demonstrate that, by rebuilding the core modules of natural K+ channels in artificial systems, the structures, transport behaviors, and physiological functions of natural K+ channels can be mimicked in synthetic channels. [ABSTRACT FROM AUTHOR]

A class of artificial K+ channels formed by pillararene‐cyclodextrin hybrid molecules have been designed and synthesized. These channels efficiently inserted into lipid bilayers and displayed high selectivity for K+ over Na+ in fluorescence and electrophysiological experiments. The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel showed specific transmembrane transport preference for K+ over all alkali metal ions (selective sequence: K+ > Cs+ > Rb+ > Na+ > Li+), and is rarely observed for artificial K+ channels. The high selectivity of this artificial channel for K+ over Na+ ensures specific transmembrane translocation of K+, and generated stable membrane potential across lipid bilayers. Old pals: A pillararene‐cyclodextrin hybrid molecule with artificial K+ channel function is presented. The cation transport selectivity of the artificial channel is tunable. The high selectivity of this artificial channel for K+ over Na+ ensures specific transmembrane translocation of K+, and generated a stable membrane potential across lipid bilayers. [ABSTRACT FROM AUTHOR]