Related Experiment Videos
Cardiomyocytes in culture--a model to study the cellular actions of amiodarone
G Kessler-Icekson1, H Schlesinger, M Djaldetti
1Felsenstein Medical Research Center, Petah Tikva, Israel.
Abstract:
The extensive use of amiodarone as an anti-arrhythmic drug is hampered by numerous side effects and by insufficient knowledge of its cellular action. The use of cell cultures for studying the mechanism of amiodarone action has been questioned, since available information has indicated that the doses employed for the experiments induce cell damage. We have defined conditions to obtain the amiodarone effect on cardiac cells in culture with no detectable damage. Amiodarone, 1 microg/ml, a concentration comparable to serum levels of the drug in acute and chronically treated humans and rats, reduces cell contractions, modifies membrane electrical properties accordingly, increases ATP content, but does not alter cell substructure or change enzyme activities. We strongly support the use of cell cultures for studying the cellular action(s) of amiodarone and offer conditions suitable for such experiments.
Insights
This study establishes optimal conditions for using cardiac cell cultures to investigate amiodarone's effects. Researchers can now study amiodarone's anti-arrhythmic mechanisms without causing cellular damage.
Area of Science:
- Pharmacology and Toxicology
- Cell Biology
- Cardiovascular Research
Background:
- Amiodarone is a widely used anti-arrhythmic medication.
- Its clinical application is limited by side effects and incomplete understanding of its cellular mechanisms.
- Previous studies using cell cultures were questioned due to induced cell damage at experimental doses.
Purpose of the Study:
- To define conditions for studying amiodarone's cellular effects on cardiac cells in culture without causing damage.
- To validate the utility of cell cultures for amiodarone mechanism research.
Main Methods:
- Cardiac cells were cultured under specific conditions.
- Amiodarone was applied at a concentration of 1 microg/ml, comparable to therapeutic serum levels.
- Cellular responses including contractions, electrical properties, ATP content, cell substructure, and enzyme activities were assessed.
Main Results:
- Amiodarone at 1 microg/ml reduced cell contractions and altered membrane electrical properties.
- A significant increase in cellular ATP content was observed.
- No detectable damage to cell substructure or changes in enzyme activities were found.
Conclusions:
- The study successfully identified conditions for amiodarone research in cardiac cell cultures without inducing cytotoxicity.
- Cardiac cell cultures are a suitable model for investigating the cellular actions of amiodarone.
- These findings support the use of this model for future amiodarone mechanism studies.