ArticleProceedings of the National Academy of Sciences of the United States of America2014
hERG 1b is critical for human cardiac repolarization.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 105 citations in OpenAlex.
- The PAS domain directly regulates hERG channel gating in patch-clamp fluorometry recordings.Biophysical journal · 2026Article
- Sudden death-associated KCNH2 variants exert opposing effects on a nuclear subdomain of the cardiac potassium channel hERG1.The Journal of biological chemistry · 2026Article
- An ER retention motif controls the heteromeric stoichiometry of hERG1a/1b channels.bioRxiv : the preprint server for biology · 2026Article
- The role of iPSC research for insight into inherited arrhythmia conditions.Heart rhythm · 2025Review
- Sudden Death-AssociatedbioRxiv : the preprint server for biology · 2025Article
- Adverse drug reaction profiles of histone deacetylase inhibitors.Scientific reports · 2025Article
- An Allosteric Model for Electromechanical Coupling in Cardiac CNBD Channels.bioRxiv : the preprint server for biology · 2025Article
- A privileged ER compartment for posttranslational heteromeric assembly of an ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A privileged ER compartment for post-translational heteromeric assembly of an ion channel.bioRxiv : the preprint server for biology · 2025Article
- ERG1A KScientific reports · 2025Article
- Long QT Interval Syndrome and Female Sex-Review and Case Report.Reports (MDPI) · 2025Article
- CardioGenAI: a machine learning-based framework for re-engineering drugs for reduced hERG liability.Journal of cheminformatics · 2025Article
- Novel Triazeneindole Antibiotics: Synthesis and Hit-to-Lead Optimization.International journal of molecular sciences · 2025Article
- A PAS-targeting hERG1 activator reduces arrhythmic events in Jervell and Lange-Nielsen syndrome patient-derived hiPSC-CMs.JCI insight · 2025Article
- Integrating drug effects on individual cardiac ionic currents and cardiac action potentials to understand nonclinical translation to clinical ECG changes.Frontiers in pharmacology · 2025Article
- Mechanistic Relevance of Ventricular Arrhythmias in Heart Failure with Preserved Ejection Fraction.International journal of molecular sciences · 2024Review
- Development of an Absolute Quantification Method for hERG Using PRM with Single Isotopologue in-Sample Calibration.ACS omega · 2024Article
- An intracellular hydrophobic nexus critical for hERG1 channel slow deactivation.Biophysical journal · 2024Article
- Zebrafish cardiac repolarization does not functionally depend on the expression of the hERG1b-like transcript.Pflugers Archiv : European journal of physiology · 2024Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The human ether-à-go-go-related gene (hERG; or KCNH2) encodes the voltage-gated potassium channel underlying IKr, a repolarizing current in the heart. Mutations in KCNH2 or pharmacological agents that reduce IKr slow action potential (AP) repolarization and can trigger cardiac arrhythmias associated with long QT syndrome. Two channel-forming subunits encoded by KCNH2 (hERG 1a and 1b) are expressed in cardiac tissue. In heterologous expression systems, these subunits avidly coassemble and exhibit biophysical and pharmacological properties distinct from those of homomeric hERG 1a channels. Despite these findings, adoption of hERG 1a/1b heteromeric channels as a model for cardiac IKr has been hampered by the lack of evidence for a direct functional role for the 1b subunit in native tissue. In this study, we measured IKr and APs at physiological temperature in cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs). We found that specific knockdown of the 1b subunit using shRNA caused reductions in 1b mRNA, 1b protein levels, and IKr magnitude by roughly one-half. AP duration was increased and AP variability was enhanced relative to controls. Early afterdepolarizations, considered cellular substrates for arrhythmia, were also observed in cells with reduced 1b expression. Similar behavior was elicited when channels were effectively converted from heteromers to 1a homomers by expressing a fragment corresponding to the 1a-specific N-terminal Per-Arnt-Sim domain, which is omitted from hERG 1b by alternate transcription. These findings establish that hERG 1b is critical for normal repolarization and that loss of 1b is proarrhythmic in human cardiac cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.