Electrophysiological Phenotyping of hiPSC-Derived Atrial Cardiomyocytes Using Automated Patch-Clamp: A Platform for Studying Atrial Inherited Arrhythmias
Highlights What are the main findings? Developed an optimized dissociation and recording protocol enabling reliable automated patch-clamp recordings of major atrial ionic currents (INa, ICaL, Ito, IKur, ISK, and If) in hiPSC-derived atrial cardiomyocytes. Demonstrated that current profiles obtained...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p20761 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=20761 |
| Access Level: | acceso abierto |
| Palabra clave: | automated patch-clamp cardiac ion channels human-induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs) arrhythmia |
| Sumario: | Highlights What are the main findings? Developed an optimized dissociation and recording protocol enabling reliable automated patch-clamp recordings of major atrial ionic currents (INa, ICaL, Ito, IKur, ISK, and If) in hiPSC-derived atrial cardiomyocytes. Demonstrated that current profiles obtained with the automated Patchliner system resemble those of native human atrial cardiomyocytes, validating the physiological relevance of the model. What are the implications of the main findings? The optimized automated patch-clamp workflow provides a robust platform for the functional characterization of ion channels and genetic variants implicated in atrial arrhythmias. This approach facilitates precision medicine applications and targeted drug development for atrial channelopathies.Highlights What are the main findings? Developed an optimized dissociation and recording protocol enabling reliable automated patch-clamp recordings of major atrial ionic currents (INa, ICaL, Ito, IKur, ISK, and If) in hiPSC-derived atrial cardiomyocytes. Demonstrated that current profiles obtained with the automated Patchliner system resemble those of native human atrial cardiomyocytes, validating the physiological relevance of the model. What are the implications of the main findings? The optimized automated patch-clamp workflow provides a robust platform for the functional characterization of ion channels and genetic variants implicated in atrial arrhythmias. This approach facilitates precision medicine applications and targeted drug development for atrial channelopathies.Abstract Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a robust platform for modelling inherited cardiac disorders. Comparative analysis of ion channel activity in patient-specific and isogenic control lines provides critical insights into the molecular mechanisms underlying channelopathies and arrhythmias. Atrial-specific hiPSC-CMs (hiPSC-aCMs) exhibit distinct electrophysiological properties governed by unique ion channel expression profiles, underscoring the need for optimized methodologies to record atrial ionic currents accurately. Here, we characterized the electrophysiological features of hiPSC-aCMs using the Nanion Patchliner automated patch-clamp system. An optimized cell dissociation protocol was developed to enhance cell integrity and seal formation, while tailored intra- and extracellular solutions were employed to isolate specific ionic currents. Using this approach, we reliably recorded major atrial currents, including the sodium current (INa), L-type calcium current (ICaL), transient outward potassium current (Ito), ultrarapid component of the delayed rectifier current (IKur), small-conductance calcium-activated potassium current (ISK), and pacemaker funny current (If). The resulting current profiles were reproducible and consistent with those observed in native atrial cardiomyocytes. These findings establish the feasibility of the automated electrophysiological characterization of ion channels in hiPSC-aCMs. This platform enables more efficient investigation of pathogenic variants and facilitates the development of targeted therapeutics for atrial arrhythmias and related channelopathies. |
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