Chen Changming, Wu Jianguo, Qin Chunlian, Qiu Yong, Jiang Nan, Wang Qifei, Liu Mengxue, Jiang Deming, Yuan Qunchen, Wei Xinwei, Zhuang Liujing, Wang Ping
Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou, 310027, China.
The MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou, 310027, China.
Microsyst Nanoeng. 2025 Aug 4;11(1):147. doi: 10.1038/s41378-025-00985-5.
Bitter receptors were initially identified within the gustatory system. In recent years, bitter receptors have been found in various non-gustatory tissues, including the cardiovascular system, where they participate in diverse physiological processes. To investigate the electrophysiological and potential therapeutic implications of bitter receptors, we have developed a highly sensitive, multifunctional planar-electroporated cell biosensor (PECB) for high-throughput evaluation of the effects of bitter substances on cardiomyocytes. The PECB demonstrated the capability for high-throughput, stable, and reproducible detection of intracellular action potentials (IAPs). In comparison to conventional biosensors that utilize extracellular action potentials (EAPs) for data analysis, the IAPs recorded by the PECB provided high-resolution insights into action potentials, characterized by increased amplitudes and an enhanced signal-to-noise ratio (SNR). The PECB successfully monitored IAPs induced by the activation of bitter receptors by using three bitter substances: diphenidol, denatonium benzoate, and arbutin in cardiomyocytes. To further assess the drug development ability of our PECB, we established an in vitro long QT syndrome (LQTS) model to investigate the potential therapeutic effects of arbutin. The results indicated that arbutin altered the electrophysiological properties of cardiomyocytes and significantly shortened the repolarization time in the LQTS model. Moreover, it demonstrated its potential mechanistic pathway by activating bitter receptors to modulate cardiac ion channel activities. The developed PECB provides an effective platform for high-throughput screening of substrates of bitter receptors for the treatment of heart disease, presenting new opportunities for the development of antiarrhythmic therapies.
苦味受体最初是在味觉系统中被识别出来的。近年来，已在包括心血管系统在内的各种非味觉组织中发现了苦味受体，它们参与多种生理过程。为了研究苦味受体的电生理及潜在治疗意义，我们开发了一种高度灵敏的多功能平面电穿孔细胞生物传感器（PECB），用于高通量评估苦味物质对心肌细胞的影响。PECB展示了对细胞内动作电位（IAP）进行高通量、稳定且可重复检测的能力。与利用细胞外动作电位（EAP）进行数据分析的传统生物传感器相比，PECB记录的IAP提供了对动作电位的高分辨率洞察，其特征为幅度增加和信噪比（SNR）提高。PECB通过使用三种苦味物质——地芬尼多、苯甲地那铵和熊果苷，成功监测了心肌细胞中苦味受体激活所诱导的IAP。为了进一步评估我们的PECB的药物开发能力，我们建立了体外长QT综合征（LQTS）模型来研究熊果苷的潜在治疗效果。结果表明，熊果苷改变了心肌细胞的电生理特性，并在LQTS模型中显著缩短了复极时间。此外，它通过激活苦味受体来调节心脏离子通道活性，展示了其潜在的作用机制途径。所开发的PECB为高通量筛选用于治疗心脏病的苦味受体底物提供了一个有效平台，为抗心律失常疗法的开发带来了新机遇。
