ArticleCirculation research2009
Antiarrhythmic drug-induced internalization of the atrial-specific k+ channel kv1.5.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- SNAP25-dependent membrane trafficking of the Kv1.5 channel regulates the onset of atrial fibrillation.Nature communications · 2025Article
- Rational design, synthesis, and evaluation of novel polypharmacological compounds targeting NaThe Journal of biological chemistry · 2025Article
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Unravelling NovelInternational journal of molecular sciences · 2023Article
- Insights of Endocytosis Signaling in Health and Disease.International journal of molecular sciences · 2023Review
- KInternational journal of molecular sciences · 2021Article
- Review
- Two New Neo-debromoaplysiatoxins-A Pair of Stereoisomers Exhibiting Potent Kv1.5 Ion Channel Inhibition Activities.Marine drugs · 2019Article
- The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart.Journal of diabetes research · 2018Article
- Over-expression of microRNA-1 causes arrhythmia by disturbing intracellular trafficking system.Scientific reports · 2017Article
- Genistein and tyrphostin AG556 decrease ultra-rapidly activating delayed rectifier KBritish journal of pharmacology · 2017Article
- Ion Channel Trafficking: Control of Ion Channel Density as a Target for Arrhythmias?Frontiers in physiology · 2017Review
- Blockade of Kv1.5 channels by the antidepressant drug sertraline.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2016Article
- Polycomb-dependent repression of the potassium channel-encoding gene KCNA5 promotes cancer cell survival under conditions of stress.Oncogene · 2015Article
- Role for myosin-V motor proteins in the selective delivery of Kv channel isoforms to the membrane surface of cardiac myocytes.Circulation research · 2014Article
- Improved functional expression of human cardiac kv1.5 channels and trafficking-defective mutants by low temperature treatment.PloS one · 2014Article
- Shear stress triggers insertion of voltage-gated potassium channels from intracellular compartments in atrial myocytes.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Trafficking of intermediate (KCa3.1) and small (KCa2.x) conductance, Ca(2+)-activated K(+) channels: a novel target for medicinal chemistry efforts?ChemMedChem · 2012Review
- Redox-sensitive sulfenic acid modification regulates surface expression of the cardiovascular voltage-gated potassium channel Kv1.5.Circulation research · 2012Article
- Dynamic reciprocity of sodium and potassium channel expression in a macromolecular complex controls cardiac excitability and arrhythmia.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Conventional antiarrhythmic drugs target the ion permeability of channels, but increasing evidence suggests that functional ion channel density can also be modified pharmacologically. Kv1.5 mediates the ultrarapid potassium current (I(Kur)) that controls atrial action potential duration. Given the atrial-specific expression of Kv1.5 and its alterations in human atrial fibrillation, significant effort has been made to identify novel channel blockers. In this study, treatment of HL-1 atrial myocytes expressing Kv1.5-GFP with the class I antiarrhythmic agent quinidine resulted in a dose- and temperature-dependent internalization of Kv1.5, concomitant with channel block. This quinidine-induced channel internalization was confirmed in acutely dissociated neonatal myocytes. Channel internalization was subunit-dependent, activity-independent, stereospecific, and blocked by pharmacological disruption of the endocytic machinery. Pore block and channel internalization partially overlap in the structural requirements for drug binding. Surprisingly, quinidine-induced endocytosis was calcium-dependent and therefore unrecognized by previous biophysical studies focused on isolating channel-drug interactions. Importantly, whereas acute quinidine-induced internalization was reversible, chronic treatment led to channel degradation. Together, these data reveal a novel mechanism of antiarrhythmic drug action and highlight the possibility for new agents that selectively modulate the stability of channel protein in the membrane as an approach for treating cardiac arrhythmias.
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Registered trials
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