Bionic Potassium Ion Channel in Live Cells Repairs Cardiomyocyte Function,Journal of the American Chemical Society

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Bionic Potassium Ion Channel in Live Cells Repairs Cardiomyocyte Function
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2024-07-09 , DOI: 10.1021/jacs.4c03203
Xuejie Shen ₁ , Qingqing Lu ₂ , Tianhuan Peng ₁ , Yun Zhang ₃ , Weihong Tan ₁ , Yanbing Yang ₂ , Jie Tan ₁ , Quan Yuan _{1,

2}

Affiliation

The disturbance of potassium current in cardiac myocytes caused by potassium channel dysfunction can lead to cardiac electrophysiological disorders, resulting in associated cardiovascular diseases. The emergence of artificial potassium ion channels opens up a way to replace dysfunctional natural ion channels and cure related diseases. However, bionic potassium ion channels have not been introduced into living cells to regulate cell function. One of the biggest challenges is that when the bionic channel fuses with the cell, it is difficult to control the inserting angle of the bionic potassium channel to ensure its penetration of the entire cell membrane. In nature, the extracellular vesicles can fuse with living cells with a completely preserved structure of vesicle protein. Inspired by this, we developed a vesicle fusion-based bionic porin (VFBP), which integrates bionic potassium ion channels into cardiomyocytes to replace damaged potassium ion channels. Theoretical and experimental results show that the inserted bionic ion channels have a potassium ion transport rate comparable to that of natural ion channels, which can restore the potassium ion outflow in cardiomyocytes and repair the abnormal action potential and excitation–contraction coupling of cardiomyocytes. Therefore, the bionic potassium ion channel system based on membrane fusion is expected to become the research object in many fields such as ultrafast ion transport, transmembrane delivery, and channelopathies treatment.

中文翻译：

活细胞中的仿生钾离子通道修复心肌细胞功能

钾通道功能障碍引起心肌细胞钾电流紊乱，可导致心脏电生理紊乱，引发相关心血管疾病。人工钾离子通道的出现为替代功能失调的天然离子通道并治疗相关疾病开辟了一条途径。然而，仿生钾离子通道尚未被引入活细胞中来调节细胞功能。最大的挑战之一是仿生通道与细胞融合时，很难控制仿生钾通道的插入角度以保证其穿透整个细胞膜。在自然界中，细胞外囊泡可以与活细胞融合，并完整保留囊泡蛋白的结构。受此启发，我们开发了一种基于囊泡融合的仿生孔蛋白（VFBP），它将仿生钾离子通道整合到心肌细胞中以替代受损的钾离子通道。理论和实验结果表明，插入的仿生离子通道具有与天然离子通道相当的钾离子转运速率，可以恢复心肌细胞内钾离子的流出，修复心肌细胞异常的动作电位和兴奋收缩耦合。因此，基于膜融合的仿生钾离子通道系统有望成为超快离子传输、跨膜递送、离子通道病治疗等多个领域的研究对象。

更新日期：2024-07-09

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