Electrophysiological Characterization of Spontaneously Contracting Cell Aggregates Obtained from Rainbow Trout Larvae with Multielectrode Arrays
Background/Aims: Safety pharmacology requires novel model systems for the detection of cardiac side effects. Ranging from cell-based systems to model organisms, no model available to date reflects the complexity of the human heart and evokes the great need for improved and more affordable systems. M...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2013-11-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/356576 |
| _version_ | 1828160024538513408 |
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| author | Julia M. Mehnert Matthias Brandenburger Bianka Grunow |
| author_facet | Julia M. Mehnert Matthias Brandenburger Bianka Grunow |
| author_sort | Julia M. Mehnert |
| collection | DOAJ |
| description | Background/Aims: Safety pharmacology requires novel model systems for the detection of cardiac side effects. Ranging from cell-based systems to model organisms, no model available to date reflects the complexity of the human heart and evokes the great need for improved and more affordable systems. Many drugs interact with hERG potassium channels and consequently cause life threatening ventricular arrhythmias, further highlighting the importance of suitable model systems. Methods: Spontaneously Contracting Cell aggregates (SCC) as a 3D in vitro heart-syncytium obtained from rainbow trout larvae represent a novel model system for cardiac safety pharmacology. SCCs can be harvested cost-effectively and kept in culture for several weeks while retaining their functionality and displaying contraction rates similar to the human heart. Results: Extracellular field potential recordings with multielectrode arrays revealed significant prolongation of field potential duration upon administration of common hERG potassium channel blockers. Infusion of 1 µM Dofetilide and 10 µM Terfenadine prolonged field potentials 10 fold and 2 fold, respectively. In addition, SCCs enabled analysis of autonomous contraction frequencies. Conclusion: Thus, SCCs represent a novel and low-cost cardiac model system of the human heart for application in safety pharmacology. |
| first_indexed | 2024-04-12T00:11:38Z |
| format | Article |
| id | doaj.art-99a3e959d1c84541a80eeeae9e74c6fd |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-12T00:11:38Z |
| publishDate | 2013-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-99a3e959d1c84541a80eeeae9e74c6fd2022-12-22T03:55:57ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782013-11-013251374138510.1159/000356576356576Electrophysiological Characterization of Spontaneously Contracting Cell Aggregates Obtained from Rainbow Trout Larvae with Multielectrode ArraysJulia M. MehnertMatthias BrandenburgerBianka GrunowBackground/Aims: Safety pharmacology requires novel model systems for the detection of cardiac side effects. Ranging from cell-based systems to model organisms, no model available to date reflects the complexity of the human heart and evokes the great need for improved and more affordable systems. Many drugs interact with hERG potassium channels and consequently cause life threatening ventricular arrhythmias, further highlighting the importance of suitable model systems. Methods: Spontaneously Contracting Cell aggregates (SCC) as a 3D in vitro heart-syncytium obtained from rainbow trout larvae represent a novel model system for cardiac safety pharmacology. SCCs can be harvested cost-effectively and kept in culture for several weeks while retaining their functionality and displaying contraction rates similar to the human heart. Results: Extracellular field potential recordings with multielectrode arrays revealed significant prolongation of field potential duration upon administration of common hERG potassium channel blockers. Infusion of 1 µM Dofetilide and 10 µM Terfenadine prolonged field potentials 10 fold and 2 fold, respectively. In addition, SCCs enabled analysis of autonomous contraction frequencies. Conclusion: Thus, SCCs represent a novel and low-cost cardiac model system of the human heart for application in safety pharmacology.http://www.karger.com/Article/FullText/356576QT drugsCardiac model systemPharmacologyElectrophysiology |
| spellingShingle | Julia M. Mehnert Matthias Brandenburger Bianka Grunow Electrophysiological Characterization of Spontaneously Contracting Cell Aggregates Obtained from Rainbow Trout Larvae with Multielectrode Arrays Cellular Physiology and Biochemistry QT drugs Cardiac model system Pharmacology Electrophysiology |
| title | Electrophysiological Characterization of Spontaneously Contracting Cell Aggregates Obtained from Rainbow Trout Larvae with Multielectrode Arrays |
| title_full | Electrophysiological Characterization of Spontaneously Contracting Cell Aggregates Obtained from Rainbow Trout Larvae with Multielectrode Arrays |
| title_fullStr | Electrophysiological Characterization of Spontaneously Contracting Cell Aggregates Obtained from Rainbow Trout Larvae with Multielectrode Arrays |
| title_full_unstemmed | Electrophysiological Characterization of Spontaneously Contracting Cell Aggregates Obtained from Rainbow Trout Larvae with Multielectrode Arrays |
| title_short | Electrophysiological Characterization of Spontaneously Contracting Cell Aggregates Obtained from Rainbow Trout Larvae with Multielectrode Arrays |
| title_sort | electrophysiological characterization of spontaneously contracting cell aggregates obtained from rainbow trout larvae with multielectrode arrays |
| topic | QT drugs Cardiac model system Pharmacology Electrophysiology |
| url | http://www.karger.com/Article/FullText/356576 |
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