Stem-cell based in vitro differentiation for disease modeling offers great value to explore the molecular and functional underpinnings driving many types of cardiomyopathy and congenital heart diseases. Nevertheless, one major caveat in the application of in vitro differentiation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) involves the immature phenotype of the CMs. Most of the existing methods need complex apparatus and require laborious procedures in order to monitor the cardiac differentiation/maturation process and often result in cell death. Here we developed an intrinsic color sensing system utilizing a microgroove structural color methacrylated gelatin film, which allows us to monitor the cardiac differentiation process of hiPSC-derived cardiac progenitor cells in real time. Subsequently this system can be employed as an assay system to live monitor induced functional changes on hiPSC-CMs stemming from drug treatment, the effects of which are simply revealed through color diversity. Our research shows that early intervention of cardiac differentiation through simple physical cues can enhance cardiac differentiation and maturation to some extent. Our system also simplifies the previous complex experimental processes for evaluating the physiological effects of successful differentiation and drug treatment and lays a solid foundation for future transformational applications.
Background: Ventricular-like human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exhibit the electrophysiological characteristics of spontaneous beating. Previous studies demonstrated that dexmedetomidine (DMED), a highly selective and widely used α 2 -adrenoceptor agonist for sedation, analgesia, and stress management, may induce antiarrhythmic effects, especially ventricular tachycardia.However, the underlying mechanisms of the DMED-mediated antiarrhythmic effects remain to be fully elucidated.Methods: A conventional patch-clamp recording method was used to investigate the direct effects of DMED on spontaneous action potentials, pacemaker currents (I f ), potassium (K + ) channel currents (I K1 and I Kr ), sodium (Na + ) channel currents (I Na ), and calcium (Ca 2+ ) channel currents (I Ca ) in ventricular-like hiPSC-CMs.Results: DMED dose-dependently altered the frequency of ventricular-like spontaneous action potentials with a half-maximal inhibitory concentration (IC 50 ) of 27.9 μM (n=6) and significantly prolonged the action potential duration at 90% repolarization (APD 90 ). DMED also inhibited the amplitudes of the I Na and I Ca without affecting the activation and inactivation curves of these channels. DMED decreased the time constant of the Na + and Ca 2+ channel activation at potential -40 to -20 mv, and -20 mv. DMED increased the time constant of inactivation of the Na + and Ca 2+ channels. However, DMED did not affect the I K1 , I Kr , I f , and their current-voltage relationship. The ability of DMED to decrease the spontaneous action potential frequency and the Na + and Ca 2+ channel amplitudes, were not blocked by yohimbine, idazoxan, or phentolamine.
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