ArticleToxicology and applied pharmacology2013
Mechanism of HERG potassium channel inhibition by tetra-n-octylammonium bromide and benzethonium chloride.
Article in Toxicology and applied pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 17 citations in OpenAlex.
- Optical control of the cardiac rhythm with photoswitchable NaNature communications · 2026Article
- Ketamine preservative benzethonium chloride potentiates hippocampal synaptic transmission and binds neurotransmitter receptors and transporters.Neuropharmacology · 2023Review
- Virtual screening of DrugBank database for hERG blockers using topological Laplacian-assisted AI models.Computers in biology and medicine · 2023Article
- Assessment of potassium ion channel during electric signalling in biofilm formation ofHeliyon · 2023Article
- High-Throughput Chemical Screening and Structure-Based Models to Predict hERG Inhibition.Biology · 2022Article
- Inhibition of HERG potassium channels by domiphen bromide and didecyl dimethylammonium bromide.European journal of pharmacology · 2014Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Tetra-n-octylammonium bromide and benzethonium chloride are synthetic quaternary ammonium salts that are widely used in hospitals and industries for the disinfection and surface treatment and as the preservative agent. Recently, the activities of HERG channel inhibition by these compounds have been found to have potential risks to induce the long QT syndrome and cardiac arrhythmia, although the mechanism of action is still elusive. This study was conducted to investigate the mechanism of HERG channel inhibition by these compounds by using whole-cell patch clamp experiments in a CHO cell line stably expressing HERG channels. Tetra-n-octylammonium bromide and benzethonium chloride exhibited concentration-dependent inhibitions of HERG channel currents with IC(50) values of 4nM and 17nM, respectively, which were also voltage-dependent and use-dependent. Both compounds shifted the channel activation I-V curves in a hyperpolarized direction for 10-15mV and accelerated channel activation and inactivation processes by 2-fold. In addition, tetra-n-octylammonium bromide shifted the inactivation I-V curve in a hyperpolarized direction for 24.4mV and slowed the rate of channel deactivation by 2-fold, whereas benzethonium chloride did not. The results indicate that tetra-n-octylammonium bromide and benzethonium chloride are open-channel blockers that inhibit HERG channels in the voltage-dependent, use-dependent and state-dependent manners.
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