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High throughput measurement of Ca²âº dynamics for drug risk assessment in human stem cell-derived cardiomyocytes by kinetic image cytometry.
Cerignoli, Fabio; Charlot, David; Whittaker, Ross; Ingermanson, Randy; Gehalot, Piyush; Savchenko, Alex; Gallacher, David J; Towart, Rob; Price, Jeffrey H; McDonough, Patrick M; Mercola, Mark.
Affiliation
  • Cerignoli F; Sanford-Burnham Medical Research Institute, 10901N. Torrey Pines Road, La Jolla, CA 92037, USA.
J Pharmacol Toxicol Methods ; 66(3): 246-56, 2012.
Article in 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 Ca²âº indicators. The KIC instrument simultaneously records and analyzes intracellular calcium concentration [Ca²âº](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 Ca²âº 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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Calcium / Myocytes, Cardiac / Drug-Related Side Effects and Adverse Reactions / High-Throughput Screening Assays Type of study: Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Animals / Humans Language: En Journal: J Pharmacol Toxicol Methods Journal subject: FARMACOLOGIA / TOXICOLOGIA Year: 2012 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Calcium / Myocytes, Cardiac / Drug-Related Side Effects and Adverse Reactions / High-Throughput Screening Assays Type of study: Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Animals / Humans Language: En Journal: J Pharmacol Toxicol Methods Journal subject: FARMACOLOGIA / TOXICOLOGIA Year: 2012 Document type: Article Affiliation country: United States