Key result
Generalised Eyring model outperforms standard Q10 coefficients in capturing hERG temperature-dependent kinetics.
Why the study?
Temperature-dependent changes in voltage-dependent ion channel kinetics are commonly represented with Q10 coefficients or an Eyring relationship, but the validity of these representations for hERG channel kinetics was uncertain.
Population
CHO cells over-expressing hERG1a
Comparison
hERG kinetics at five distinct temperatures between 25 and 37 °C
Design
Preclinical study using a 15 second information-rich optimised protocol on a 384-well automated patch clamp platform
Authors
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May mislead hERG-based drug safety extrapolations using Q10; leaves open generalised Eyring models for accurate kinetics.
Standard Q10 coefficients and Eyring formulations inadequately describe the temperature dependence of hERG channel kinetics, highlighting the need for direct measurement or generalized Eyring models to avoid misleading extrapolations in drug safety assessment.
Lei et al. (2019) studied hERG channel kinetics (n=429). Temperature variation (25 to 37°C) vs. Standard Q10 extrapolations was evaluated on Fit of kinetic parameters to Generalised Eyring vs Q10 relationships. The temperature dependency of hERG kinetic parameters is poorly represented by standard Q10 coefficients but broadly follows a Generalised Eyring relationship.
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