March 15, 2018Scientific ReportsOpen Access

Investigating the state dependence of drug binding in hERG channels using a trapped-open channel phenotype

View Full Paper

Ask AI

Bookmark

Structured PICO

Population

Xenopus laevis oocytes expressing wild-type and mutant (I663P, I663P/S620T) hERG channels

Intervention

Application of hERG blockers cisapride and terfenadine at varying membrane voltages (-80 mV to +40 mV)

Comparator

Wild-type hERG channels and varying membrane voltages

Outcome

Drug binding affinity (IC50) and percentage block at different membrane voltagessurrogate

Inactivation is not a major determinant of cisapride or terfenadine binding in hERG channels, challenging previous models of drug-channel interactions.

Limitations

The slope of the voltage-dependence of inactivation in hERG I663P channels was steeper than that observed in WT channels, which suggests that the voltage-sensitivity of inactivation may be enhanced in trapped-open channels

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Block by terfenadine/cisapride is inactivation-independent; challenges prior hERG models but hypothesis-generating in animal data.

Cite This Study

Thouta et al. (2018) studied this question.

synapsesocial.com/papers/6a83a212a3cef8348e9966d9 https://doi.org/10.1038/s41598-018-23346-x

View Full Paper

Ask AI

Bookmark

Investigating the state dependence of drug binding in hERG channels using a trapped-open channel phenotype

Structured PICO

Limitations

Discussion

Implication

Cite This Study

Investigating the state dependence of drug binding in hERG channels using a trapped-open channel phenotype

Structured PICO

Limitations

Discussion

Implication

Cite This Study

Also Consider

Also Consider