Reliable identification of cardiac conduction abnormalities in drug discovery using automated patch clamp II: Best practices for Nav1.5 peak current in a high throughput screening environment

Journal of Pharmacological and Toxicological Methods(2021)

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摘要
•Experimental parameters influencing compound potency on NaV1.5 using automated patch clamp are investigated.•Voltage protocol affects IC50 of compounds acting on NaV1.5 and should be carefully considered.•Temperature can influence IC50 and should be carefully controlled. Where possible, recordings should be performed at 37 °C.•A minimum incubation time of 5 min should be employed to ensure steady state is reached.•With standardized protocols, data can be compared across APC platforms and with literature values.
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关键词
Automated patch clamp,NaV1.5,Ion channels,Safety pharmacology,Comprehensive in vitro Proarrhythmia assay (CiPA),Safety assessment,Cardiovascular safety,Proarrhythmic risk assessment,HTS
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