ArticleBiophysical journal2015
Kinetic model for NS1643 drug activation of WT and L529I variants of Kv11.1 (hERG1) potassium channel.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- NS1643 enhances the activity of T1019PfsX38 and Q1070X hERG channels associated with long QT syndrome type 2.Pflugers Archiv : European journal of physiology · 2026Article
- Pharmacological activation of the hERG KJournal of arrhythmia · 2022Review
- Modeling the kinetics of heteromeric potassium channels.Frontiers in cellular neuroscience · 2022Article
- Calibration of ionic and cellular cardiac electrophysiology models.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Four Ways to Fit an Ion Channel Model.Biophysical journal · 2019Article
- Functional study of a KCNH2 mutant: Novel insights on the pathogenesis of the LQT2 syndrome.Journal of cellular and molecular medicine · 2019Article
- Determinants of Isoform-Specific Gating Kinetics of hERG1 Channel: Combined Experimental and Simulation Study.Frontiers in physiology · 2018Article
- Potassium channels in the heart: structure, function and regulation.The Journal of physiology · 2017Review
- Molecular Pathophysiology of Congenital Long QT Syndrome.Physiological reviews · 2017Review
- Role of the pH in state-dependent blockade of hERG currents.Scientific reports · 2016Article
- Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology.Cardiac electrophysiology clinics · 2016Review
- Activation of HERG channels: opening new applications for the biophysics of antiarrhythmic therapy.Biophysical journal · 2015Article
- NS1643 interacts around L529 of hERG to alter voltage sensor movement on the path to activation.Biophysical journal · 2015Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Congenital and acquired (drug-induced) forms of the human long-QT syndrome are associated with alterations in Kv11.1 (hERG) channel-controlled repolarizing IKr currents of cardiac action potentials. A mandatory drug screen implemented by many countries led to a discovery of a large group of small molecules that can activate hERG currents and thus may act as potent antiarrhythmic agents. Despite significant progress in identification of channel activators, little is known about their mechanism of action. A combination of electrophysiological studies with molecular and kinetic modeling was used to examine the mechanism of a model activator (NS1643) action on the hERG channel and its L529I mutant. The L529I mutant has gating dynamics similar to that of wild-type while its response to application of NS1643 is markedly different. We propose a mechanism compatible with experiments in which the model activator binds to the closed (C3) and open states (O). We suggest that NS1643 is affecting early gating transitions, probably during movements of the voltage sensor that precede the opening of the activation gate.
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