Publications by authors named "Yiqi Gong"

3 Publications

  • Page 1 of 1

Yohimbine Directly Induces Cardiotoxicity on Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Cardiovasc Toxicol 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai, 200127, China.

Yohimbine is a highly selective and potent α-adrenoceptor antagonist, which is usually treated as an adjunction for impotence, as well for weight loss and natural bodybuilding aids. However, it was recently reported that Yohimbine causes myocardial injury and controversial results were reported in the setting of cardiac diseases. Here, we used human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model system to explore electrophysiologic characterization after exposure to Yohimbine. HiPSC-CMs were differentiated by employment of inhibitory Wnt compounds. For analysis of electrophysiological properties, conventional whole-cell patch-clamp recording was used. Specifically, spontaneous action potentials, pacemaker currents (I), sodium (Na) channel (I), and calcium (Ca) channel currents (I) were assessed in hiPSC-CMs after exposure to Yohimbine. HiPSC-CMs expressed sarcomeric-α-actinin and MLC2V proteins, as well as exhibited ventricular-like spontaneous action potential waveform. Yohimbine inhibited frequency of hiPSC-CMs spontaneous action potentials and significantly prolonged action potential duration in a dose-dependent manner. In addition, rest potential, threshold potential, amplitude, and maximal diastolic potential were decreased, whereas APD/APD was prolonged. Yohimbine inhibited the amplitude of I in low doses (IC = 14.2 μM, n = 5) and inhibited I in high doses (IC = 139.7 μM, n = 5). Whereas Yohimbine did not affect the activation curves, treatment resulted in left shifts in inactivation curves of both Na and Ca channels. Here, we show that Yohimbine induces direct cardiotoxic effects on spontaneous action potentials of I and I in hiPSC-CMs. Importantly, these effects were not mediated by α-adrenoceptor signaling. Our results strongly suggest that Yohimbine directly and negatively affects electrophysiological properties of human cardiomyocytes. These findings are highly relevant for potential application of Yohimbine in patients with atrioventricular conduction disorder.
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http://dx.doi.org/10.1007/s12012-021-09709-3DOI Listing
November 2021

Dexmedetomidine exhibits antiarrhythmic effects on human-induced pluripotent stem cell-derived cardiomyocytes through a Na/Ca channel-mediated mechanism.

Ann Transl Med 2021 Mar;9(5):399

Department of Pediatric Cardiothoracic Surgery, Shanghai Children's Medical Center; School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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-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 ( ), potassium (K) channel currents ( and ), sodium (Na) channel currents ( ), and calcium (Ca) channel currents ( ) 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) of 27.9 µM (n=6) and significantly prolonged the action potential duration at 90% repolarization (APD). DMED also inhibited the amplitudes of the and without affecting the activation and inactivation curves of these channels. DMED decreased the time constant of the Na and Ca channel activation at potential -40 to -20 mv, and -20 mv. DMED increased the time constant of inactivation of the Na and Ca channels. However, DMED did not affect the , , , and their current-voltage relationship. The ability of DMED to decrease the spontaneous action potential frequency and the Na and Ca channel amplitudes, were not blocked by yohimbine, idazoxan, or phentolamine.

Conclusions: DMED could inhibit the frequency of spontaneous action potentials and decrease the and of hiPSC-CMs via mechanisms that were independent of the α-adrenoceptor, the imidazoline receptor, and the α-adrenoceptor. These inhibitory effects on hiPSC-CMs may contribute to the antiarrhythmic effects of DMED.
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http://dx.doi.org/10.21037/atm-20-5898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033317PMC
March 2021

Intrinsic Color Sensing System Allows for Real-Time Observable Functional Changes on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

ACS Nano 2020 07 8;14(7):8232-8246. Epub 2020 Jul 8.

Department of Pediatric Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, Shanghai 200127, China.

Stem-cell based 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 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.
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http://dx.doi.org/10.1021/acsnano.0c01745DOI Listing
July 2020
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