ArticleNaunyn-Schmiedeberg's archives of pharmacology2011
hERG K+ channel-associated cardiac effects of the antidepressant drug desipramine.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Amiodarone Advances the Apoptosis of Cardiomyocytes by Repressing Sigmar1 Expression and Blocking KCNH2-related Potassium Channels.Current molecular medicine · 2025Article
- Recording ten-fold larger IFrontiers in physiology · 2024Article
- Inhibitory Effectiveness in Delayed-Rectifier Potassium Current Caused by Vortioxetine, Known to Be a Novel Antidepressant.Biomedicines · 2022Article
- Drug-specific risk of severe QT prolongation following acute drug overdose.Clinical toxicology (Philadelphia, Pa.) · 2020Article
- Key Role of the Membrane Trafficking of Nav1.5 Channel Protein in Antidepressant-Induced Brugada Syndrome.Frontiers in physiology · 2018Article
- hERG quality control and the long QT syndrome.The Journal of physiology · 2016Review
- Pharmacological treatment with mirtazapine rescues cortical atrophy and respiratory deficits in MeCP2 null mice.Scientific reports · 2016Article
- The protease inhibitor atazanavir blocks hERG K(+) channels expressed in HEK293 cells and obstructs hERG protein transport to cell membrane.Acta pharmacologica Sinica · 2015Article
- Effect of celastrol on growth inhibition of prostate cancer cells through the regulation of hERG channel in vitro.BioMed research international · 2015Article
- Pharmacological chaperoning: a primer on mechanism and pharmacology.Pharmacological research · 2014Review
- HERG K+ channel-dependent apoptosis and cell cycle arrest in human glioblastoma cells.PloS one · 2014Article
- Differential hERG ion channel activity of ultrasmall gold nanoparticles.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Mechanisms of zolpidem-induced long QT syndrome: acute inhibition of recombinant hERG K(+) channels and action potential prolongation in human cardiomyocytes derived from induced pluripotent stem cells.British journal of pharmacology · 2013Article
- Regulation of apoptosis in HL-1 cardiomyocytes by phosphorylation of the receptor tyrosine kinase EphA2 and protection by lithocholic acid.British journal of pharmacology · 2012Article
- Desipramine prevents cardiac gap junction uncoupling.Naunyn-Schmiedeberg's archives of pharmacology · 2012Article
- Novel electrophysiological properties of dronedarone: inhibition of human cardiac two-pore-domain potassium (K2P) channels.Naunyn-Schmiedeberg's archives of pharmacology · 2012Article
- Biological Heart Rate Reduction Through Genetic Suppression of Gα(s) Protein in the Sinoatrial Node.Journal of the American Heart Association · 2012Article
- Molecular determinants of pentamidine-induced hERG trafficking inhibition.Molecular pharmacology · 2012Article
- Antidepressant-induced ubiquitination and degradation of the cardiac potassium channel hERG.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Cardiac side effects of antidepressant drugs are well recognized. Adverse effects precipitated by the tricyclic drug desipramine include prolonged QT intervals, torsade de pointes tachycardia, heart failure, and sudden cardiac death. QT prolongation has been primarily attributed to acute blockade of hERG/I(Kr) currents. This study was designed to provide a more complete picture of cellular effects associated with desipramine. hERG channels were expressed in Xenopus laevis oocytes and human embryonic kidney (HEK 293) cells, and potassium currents were recorded using patch clamp and two-electrode voltage clamp electrophysiology. Ventricular action potentials were recorded from guinea pig cardiomyocytes. Protein trafficking and cell viability were evaluated in HEK 293 cells and in HL-1 mouse cardiomyocytes by immunocytochemistry, Western blot analysis, or colorimetric MTT assay, respectively. We found that desipramine reduced hERG currents by binding to a receptor site inside the channel pore. hERG protein surface expression was reduced after short-term treatment, revealing a previously unrecognized mechanism. When long-term effects were studied, forward trafficking was impaired and hERG currents were decreased. Action potential duration was prolonged upon acute and chronic desipramine exposure. Finally, desipramine triggered apoptosis in cells expressing hERG channels. Desipramine exerts at least four different cellular effects: (1) direct hERG channel block, (2) acute reduction of hERG surface expression, (3) chronic disruption of hERG trafficking, and (4) induction of apoptosis. These data highlight the complexity of hERG-associated drug effects.
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Registered trials
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.