Cellular Phenotyping
Heart failure is a dysfunction of the heart, which can often be explained at the level of cellular physiology. This is also true for cardiac arrhythmia. In our group, we have all the tools to study cellular physiology to establish e.g. genotype - phenotype relationships.
Determining the cellular phenotype of cells is done by recording their physiological characteristics. Available methods at the Department of Medical Physiology:
- Manual patch clamping and sharp micro electrode recordings
- Automated patch clamping (Nanion Patchliner with Dynamite8 system)
- Physiological recordings from live myocardial slices
- Computational modeling of cardiac electrophysiology
- Dynamic clamping (coupling biological cells to computational models in real-time)
- Micro- and macroscoping high-speed imaging of calcium and membrane voltage
- Application of optogenetic sensors and actuators (e.g. GCaMPs, ChR2)
- Total Internal Reflection Fluorescence (TIRF) microscopy for ion channel trafficking imaging
Key Publications uitklapper, klik om te openen
Lei CL, Clerx M, Whittaker DG, Gavaghan DJ, de Boer TP, Mirams GR. Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments. Philos Trans A Math Phys Eng Sci. 2020 Jun 12;378(2173):20190348. doi: 10.1098/rsta.2019.0348. Epub 2020 May 25. PMID: 32448060; PMCID: PMC7287334.
Fabbri A, Goversen B, Vos MA, van Veen TAB, de Boer TP. Required GK1 to Suppress Automaticity of iPSC-CMs Depends Strongly on IK1 Model Structure. Biophys J. 2019 Dec 17;117(12):2303-2315. doi: 10.1016/j.bpj.2019.08.040. Epub 2019 Sep 13. PMID: 31623886; PMCID: PMC6990378.
van Opbergen CJM, Koopman CD, Kok BJM, Knöpfel T, Renninger SL, Orger MB, Vos MA, van Veen TAB, Bakkers J, de Boer TP. Optogenetic sensors in the zebrafish heart: a novel in vivo electrophysiological tool to study cardiac arrhythmogenesis. Theranostics. 2018 Sep 9;8(17):4750-4764. doi: 10.7150/thno.26108. PMID: 30279735; PMCID: PMC6160779.
Goversen B, Becker N, Stoelzle-Feix S, Obergrussberger A, Vos MA, van Veen TAB, Fertig N, de Boer TP. A Hybrid Model for Safety Pharmacology on an Automated Patch Clamp Platform: Using Dynamic Clamp to Join iPSC-Derived Cardiomyocytes and Simulations of Ik1 Ion Channels in Real-Time. Front Physiol. 2018 Jan 19;8:1094. doi: 10.3389/fphys.2017.01094. PMID: 29403387; PMCID: PMC5782795.
People Involved uitklapper, klik om te openen
Contact uitklapper, klik om te openen
Teun de Boer