ArticleThe Journal of biological chemistry2013
The interaction of caveolin 3 protein with the potassium inward rectifier channel Kir2.1: physiology and pathology related to long qt syndrome 9 (LQT9).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Identification and functional analysis of a new putative caveolin-3 variant found in a patient with sudden unexplained death.Journal of biomedical science · 2014Trial
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Caveolin-3 and Caveolin-1 Interaction Decreases Channel Dysfunction Due to Caveolin-3 Mutations.International journal of molecular sciences · 2024Article
- Caveolin-3 and Caveolae regulate ventricular repolarization.Journal of molecular and cellular cardiology · 2023Article
- Role of CaArchives of toxicology · 2023Review
- Caveolin-3 prevents swelling-induced membrane damage via regulation of IBiophysical journal · 2022Article
- Caveolin-3 and Arrhythmias: Insights into the Molecular Mechanisms.Journal of clinical medicine · 2022Review
- Review
- Cardiac potassium inward rectifier Kir2: Review of structure, regulation, pharmacology, and arrhythmogenesis.Heart rhythm · 2021Review
- Genetic cause of heterogeneous inherited myopathies in a cohort of Greek patients.Molecular genetics and metabolism reports · 2020Article
- Mechanisms of Cav3-associated arrhythmia: Protein or microdomain dysfunction?International journal of cardiology · 2020Article
- Protective role of cardiac-specific overexpression of caveolin-3 in cirrhotic cardiomyopathy.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Altering integrin engagement regulates membrane localization of KJournal of cell science · 2019Article
- Long QT syndrome caveolin-3 mutations differentially modulate KThe Journal of physiology · 2019Article
- The Potassium Channel Odyssey: Mechanisms of Traffic and Membrane Arrangement.International journal of molecular sciences · 2019Review
- Ion Channel Disorders and Sudden Cardiac Death.International journal of molecular sciences · 2018Review
- Caveolin-3 Microdomain: Arrhythmia Implications for Potassium Inward Rectifier and Cardiac Sodium Channel.Frontiers in physiology · 2018Review
- Inward Rectifier Potassium Channels (Kir2.x) and Caveolin-3 Domain-Specific Interaction: Implications for Purkinje Cell-Dependent Ventricular Arrhythmias.Circulation. Arrhythmia and electrophysiology · 2018Article
- Voltage-Gated Sodium Channel β1/β1B Subunits Regulate Cardiac Physiology and Pathophysiology.Frontiers in physiology · 2018Review
- Golgin-97 Targets Ectopically Expressed Inward Rectifying Potassium Channel, Kir2.1, to theFrontiers in physiology · 2018Article
Corrections and comments
- Erratum issuedTan, Bihua [corrected to Tan, Bi-Hua]
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in CAV3 cause LQT syndrome 9 (LQT9). A previously reported LQT9 patient had prominent U waves on ECG, a feature that has been correlated with Kir2.1 loss of function. Our objective was to determine whether caveolin 3 (Cav3) associates with Kir2.1 and whether LQT9-associated CAV3 mutations affect the biophysical properties of Kir2.1. Kir2.1 current (IK1) density was measured using the whole-cell voltage clamp technique. WT-Cav3 did not affect IK1. However, F97C-Cav3 and T78M-Cav3 decreased IK1 density significantly by ∼60%, and P104L-Cav3 decreased IK1 density significantly by ∼30% at -60 mV. Immunostained rat heart cryosections and HEK293 cells cotransfected with Kir2.1 and WT-Cav3 both demonstrated colocalization of Kir2.1 and WT-Cav3 by confocal imaging. Cav3 coimmunoprecipitated with Kir2.1 in human ventricular myocytes and in heterologous expression systems. Additionally, FRET efficiency was highly specific, with a molecular distance of 5.6 ± 0.4 nm, indicating close protein location. Colocalization experiments found that Cav3 and Kir2.1 accumulated in the Golgi compartment. On-cell Western blot analysis showed decreased Kir2.1 cell surface expression by 60% when expressed with F97C-Cav3 and by 20% when expressed with P104L-Cav3 compared with WT-Cav3. This is the first report of an association between Cav3 and Kir2.1. The Cav3 mutations F97C-Cav3, P104L-Cav3, and T78M-Cav3 decreased IK1 density significantly. This effect was related to a reduced cell surface expression of Kir2.1. Kir2.1 loss of function is additive to the increase described previously in late INa, prolonging repolarization and leading to arrhythmia generation in Cav3-mediated LQT9.
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