ArticleThe Journal of clinical investigation2009
Extracellular K+ concentration controls cell surface density of IKr in rabbit hearts and of the HERG channel in human cell lines.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
74 citing papers in PubMed, 149 citations in OpenAlex.
- Ventricular fibrillation triggered by recurrent hypoglycemia in a patient with insulinoma associated with MEN1: case report and review of literature.Endocrine journal · 2026Review
- Amiodarone irrecoverably impairs the function of human ether-a-go-go-related gene potassium channels.Molecular pharmacology · 2026Article
- Electrocardiographic Changes in Patients With Hypokalemia and Their Correlation With Serum Potassium Levels.Cureus · 2025Article
- NaInternational journal of cardiology. Heart & vasculature · 2025Article
- From genes to clinical management: A comprehensive review of long QT syndrome pathogenesis and treatment.Heart rhythm O2 · 2024Review
- Ion channel trafficking implications in heart failure.Frontiers in cardiovascular medicine · 2024Review
- A novelFrontiers in cellular neuroscience · 2024Article
- In silico analysis of the dynamic regulation of cardiac electrophysiology by KThe Journal of physiology · 2023Article
- Cardiac Arrest Following Torsades de Pointes Caused by Hypokalemia and Catecholamines in a Patient with Congenital Long QT Syndrome Type 1 After Surgical Aortic Valve Replacement: A Case Report.The American journal of case reports · 2022Article
- Metabolic and electrolyte abnormalities as risk factors in drug-induced long QT syndrome.Biophysical reviews · 2022Review
- Conductance stability and Na+ interaction with Shab K+ channels under low K+ conditions.Channels (Austin, Tex.) · 2021Article
- Review
- Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models.Frontiers in cardiovascular medicine · 2021Review
- Artificial Intelligence-Driven Algorithm for Drug Effect Prediction on Atrial Fibrillation: AnFrontiers in physiology · 2021Article
- Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias - A narrative review.Pharmacology research & perspectives · 2020Review
- Evidence for Urate Uptake Through Monocarboxylate Transporter 9 Expressed in Mammalian Cells and Its Enhancement by Heat Shock.Circulation reports · 2020Article
- Electrocardiographic manifestations in severe hypokalemia.The Journal of international medical research · 2020Article
- Overexpression of the HCN2 channel increases the arrhythmogenicity induced by hypokalemia.The journal of physiological sciences : JPS · 2019Article
- Mutation-specific peripheral and ER quality control of hERG channel cell-surface expression.Scientific reports · 2019Article
- Clinical Characteristics and Electrophysiological Mechanisms Underlying Brugada ECG in Patients With Severe Hyperkalemia.Journal of the American Heart Association · 2019Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the modulation of ion channel gating by hormones and drugs has been extensively studied, much less is known about how cell surface ion channel expression levels are regulated. Here, we demonstrate that the cell surface density of both the heterologously expressed K+ channel encoded by the human ether-a-go-go-related gene (HERG) and its native counterpart, the rapidly activating delayed rectifier K+ channel (IKr), in rabbit hearts in vivo is precisely controlled by extracellular K+ concentration ([K+]o) within a physiologically relevant range. Reduction of [K+]o led to accelerated internalization and degradation of HERG channels within hours. Confocal analysis revealed colocalization between HERG and ubiquitin during the process of HERG internalization, and overexpression of ubiquitin facilitated HERG degradation under low [K+]o. The HERG channels colocalized with a marker of multivesicular bodies during internalization, and the internalized HERG channels were targeted to lysosomes. Our results provide the first evidence to our knowledge that the cell surface density of a voltage-gated K+ channel, HERG, is regulated by a biological factor, extracellular K+. Because hypokalemia is known to exacerbate long QT syndrome (LQTS) and Torsades de pointes tachyarrhythmias, our findings provide a potential mechanistic link between hypokalemia and LQTS.
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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.