Potassium ion transport across myocardial cell membrane is essential for type 2
long QT syndrome (LQT2). However, the dysfunction of
potassium ion transport due to genetic mutations limits the
therapeutic effect in treating LQT2. Biomimetic
ion channels that selectively and efficiently transport
potassium ions across the cellular membranes are promising for the treatment of LQT2. To corroborate this, we synthesized a series of foldamer-based
ion channels with different side chains, and found a biomimetic
ion channel of K+ (BICK) with the highest transport activity among them. The selected BICK can restore
potassium ion transport and increase transmembrane
potassium ion current, thus shortening phase 3 of action potential (AP) repolarization and QT interval in LQT2. Moreover, BICK does not affect heart rate and cardiac rhythm in treating LQT2 model induced by E4031 in isolated heart as well as in guinea pigs. By restoring ion transmembrane transport tactic, biomimetic
ion channels, such as BICK, will show great potential in treating diseases related to ion transport blockade. STATEMENT OF SIGNIFICANCE: Type 2
long QT syndrome (LQT2) is a disease caused by K+ transport disorder, which can cause malignant
arrhythmia and even death. There is currently no radical cure, so it is critical to explore ways to improve K+ transmembrane transport. In this study, we report that a small-molecule biomimetic
ion channel BICK can efficiently simulate natural K+ channel
proteins on the cardiomyocyte and cure E4031-induced LQT2 in guinea pig by restoring K+ transport function for the first time. This study found that the
potassium transmembrane transport by BICK significantly reduced the QT interval, which provides a conceptually new strategy for the treatment of LQT2 disease.