ArticleHeart rhythm2011
Protein kinase C downregulates I(Ks) by stimulating KCNQ1-KCNE1 potassium channel endocytosis.
Article in Heart rhythm, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 54 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
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- Integrated Network Pharmacology and Transcriptomics Analysis to Elucidate the Mechanism of Huoxue Tongluo Qiwei Decoction in the Treatment of Erectile Dysfunction in Spontaneously Hypertensive Rats through Angii-Activated Pkcε Pathway.Combinatorial chemistry & high throughput screening · 2025Article
- The endocannabinoid ARA-S facilitates the activation of cardiac Kv7.1/KCNE1 channels from different species.Channels (Austin, Tex.) · 2024Article
- Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis.Circulation research · 2024Article
- Role of Protein Kinase C in Metabolic Regulation of Coronary Endothelial Small Conductance Calcium-Activated Potassium Channels.Journal of the American Heart Association · 2024Article
- Article
- The Phosphorylation of Kv1.3: A Modulatory Mechanism for a Multifunctional Ion Channel.Cancers · 2023Review
- The focal adhesion protein Testin modulates KCNE2 potassium channel β subunit activity.Channels (Austin, Tex.) · 2021Article
- Fluorescence Fluctuation Spectroscopy enables quantification of potassium channel subunit dynamics and stoichiometry.Scientific reports · 2021Article
- Control of Biophysical and Pharmacological Properties of Potassium Channels by Ancillary Subunits.Handbook of experimental pharmacology · 2021Article
- Neurohormonal Regulation of IJournal of the American Heart Association · 2020Review
- Review
- The auxiliary subunit KCNE1 regulates KCNQ1 channel response to sustained calcium-dependent PKC activation.PloS one · 2020Article
- Statin-specific inhibition of Rab-GTPase regulates cPKC-mediated IKs internalization.Scientific reports · 2019Article
- KCNQ1 rescues TMC1 plasma membrane expression but not mechanosensitive channel activity.Journal of cellular physiology · 2019Article
- Fluvastatin inhibits Rab5-mediated IKs internalization caused by chronic CaJournal of molecular and cellular cardiology · 2019Article
- Differences in ion channel phenotype and function between humans and animal models.Frontiers in bioscience (Landmark edition) · 2018Review
- Ubiquitination mediates Kv1.3 endocytosis as a mechanism for protein kinase C-dependent modulation.Scientific reports · 2017Article
- Dysbindin Deficiency Modifies the Expression of GABA Neuron and Ion Permeation Transcripts in the Developing Hippocampus.Frontiers in genetics · 2017Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe slow-activating cardiac repolarization K(+) current (I(Ks)), generated by the KCNQ1-KCNE1 potassium channel complex, is controlled via sympathetic and parasympathetic regulation in vivo. Inherited KCNQ1 and KCNE1 mutations predispose to ventricular fibrillation and sudden death, often triggered by exercise or emotional stress. Protein kinase C (PKC), which is activated by α1 adrenergic receptor stimulation, is known to downregulate I(Ks) via phosphorylation of KCNE1 serine 102, but the underlying mechanism has remained enigmatic. We previously showed that KCNE1 mediates dynamin-dependent endocytosis of KCNQ1-KCNE1 complexes.
objectiveThis study sought to determine the potential role of endocytosis in I(Ks) downregulation by PKC.
methodsWe utilized patch clamping and fluorescence microscopy to study Chinese hamster ovary (CHO) cells coexpressing KCNQ1, KCNE1, and wild-type or dominant-negative mutant (K44A) dynamin 2, and neonatal mouse ventricular myocytes.
resultsThe PKC activator phorbol 12-myristate 13-acetate (PMA) decreased I(Ks) density by >60% (P < .05) when coexpressed with wild-type dynamin 2 in CHO cells, but had no effect when coexpressed with K44A-dynamin 2. Thus, functional dynamin was required for downregulation of I(Ks) by PKC activation. PMA increased KCNQ1-KCNE1 endocytosis in CHO cells expressing wild-type dynamin 2, but had no effect on KCNQ1-KCNE1 endocytosis in CHO cells expressing K44A-dynamin 2, determined using the Pearson correlation coefficient to quantify endosomal colocalization of KCNQ1 and KCNE1 with internalized fluorescent transferrin. KCNE1-S102A abolished the effect of PMA on I(Ks) currents and endocytosis. Importantly, PMA similarly stimulated endocytosis of endogenous KCNQ1 and KCNE1 in neonatal mouse myocytes.
conclusionPKC activation downregulates I(Ks) by stimulating KCNQ1-KCNE1 channel endocytosis.
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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.