Temperature Dependence of hERG Blocker Pharmacology - An Automated Patch Clamp Study
Qin Chen, Nianzhen Li, Juliette Johnson, Tanner Nevill, C., Steve Smith, and Cristian Ionescu-Zanetti
Fluxion Biosciences, South San Francisco, CA
The hERG ion channel (Kv11.1) is at the center of preclinical cardiac safety assessment. Historically, patch clamp measurements that are used to assess hERG block of candidate com- pounds have been done at room temperature. While record- ing at physiological temperatures is challenging in terms of establishing and maintaining a high sealing resistance, recordings at elevated temperature are feasible using recently introduced automated patch clamp systems are capable of controlling temperature.
In this study we compare hERG current voltage relations and kinetics at different temperatures, and report observed changes in the pharmacology of known blockers using a next generation automated patch clamp platform (IonFlux).
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