<p>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.</p><p></p>