High throughput measurement of Ca²âº dynamics for drug risk assessment in human stem cell-derived cardiomyocytes by kinetic image cytometry.
J Pharmacol Toxicol Methods
; 66(3): 246-56, 2012.
Article
em En
| MEDLINE
| ID: mdl-22926323
ABSTRACT
Current methods to measure physiological properties of cardiomyocytes and predict fatal arrhythmias that can cause sudden death, such as Torsade de Pointes, lack either the automation and throughput needed for early-stage drug discovery and/or have poor predictive value. To increase throughput and predictive power of in vitro assays, we developed kinetic imaging cytometry (KIC) for automated cell-by-cell analyses via intracellular fluorescence Ca²âº indicators. The KIC instrument simultaneously records and analyzes intracellular calcium concentration [Ca²âº](i) at 30-ms resolution from hundreds of individual cells/well of 96-well plates in seconds, providing kinetic details not previously possible with well averaging technologies such as plate readers. Analyses of human embryonic stem cell and induced pluripotent stem cell-derived cardiomyocytes revealed effects of known cardiotoxic and arrhythmogenic drugs on kinetic parameters of Ca²âº dynamics, suggesting that KIC will aid in the assessment of cardiotoxic risk and in the elucidation of pathogenic mechanisms of heart disease associated with drugs treatment and/or genetic background.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Miócitos Cardíacos
/
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
/
Ensaios de Triagem em Larga Escala
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Pharmacol Toxicol Methods
Assunto da revista:
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos