ArticleThe Journal of biological chemistry2016
Reductions in the Cardiac Transient Outward K+ Current Ito Caused by Chronic β-Adrenergic Receptor Stimulation Are Partly Rescued by Inhibition of Nuclear Factor κB.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Annexin A4 Deficient Ventricular Myocytes Display Advanced Hypertrophy and Electrical Remodeling With Chronic β-Adrenoceptor Stimulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Alumina nanoparticles-induced reduction in Ito, f contributes to the occurrence of ventricular arrhythmias.BMC cardiovascular disorders · 2026Article
- The mechanism of electrical remodeling in atrial fibrillation and current research status of natural drugs and active ingredients inhibiting atrial electrical remodeling.Frontiers in cardiovascular medicine · 2026Review
- Ventricular ion channels and arrhythmias: an overview of physiology, pathophysiology and pharmacology.Medical review (2021) · 2025Review
- KCells · 2023Review
- The Emerging Role of N-Methyl-D-Aspartate (NMDA) Receptors in the Cardiovascular System: Physiological Implications, Pathological Consequences, and Therapeutic Perspectives.International journal of molecular sciences · 2023Review
- Indoxyl sulfate reduces Ito,f by activating ROS/MAPK and NF-κB signaling pathways.JCI insight · 2022Article
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- Review
- Cardiac KHandbook of experimental pharmacology · 2021Review
- Metabolic regulation of Kv channels and cardiac repolarization by Kvβ2 subunits.Journal of molecular and cellular cardiology · 2019Article
- Cardiolipotoxicity, Inflammation, and Arrhythmias: Role for Interleukin-6 Molecular Mechanisms.Frontiers in physiology · 2018Review
- Myriad roles of voltage-activated potassium channel subunit Kvβ1.1 in the heart.American journal of physiology. Heart and circulatory physiology · 2017Article
- Kvβ1.1 (AKR6A8) senses pyridine nucleotide changes in the mouse heart and modulates cardiac electrical activity.American journal of physiology. Heart and circulatory physiology · 2017Article
- Notch-Mediated Epigenetic Regulation of Voltage-Gated Potassium Currents.Circulation research · 2016Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The fast transient outward potassium current (Ito,f) plays a critical role in the electrical and contractile properties of the myocardium. Ito,f channels are formed by the co-assembly of the pore-forming α-subunits, Kv4.2 and Kv4.3, together with the accessory β-subunit KChIP2. Reductions of Ito,f are common in the diseased heart, which is also associated with enhanced stimulation of β-adrenergic receptors (β-ARs). We used cultured neonatal rat ventricular myocytes to examine how chronic β-AR stimulation decreases Ito,f. To determine which downstream pathways mediate these Ito,f changes, adenoviral infections were used to inhibit CaMKIIδc, CaMKIIδb, calcineurin, or nuclear factor κB (NF-κB). We observed that chronic β-AR stimulation with isoproterenol (ISO) for 48 h reduced Ito,f along with mRNA expression of all three of its subunits (Kv4.2, Kv4.3, and KChIP2). Inhibiting either CaMKIIδc nor CaMKIIδb did not prevent the ISO-mediated Ito,f reductions, even though CaMKIIδc and CaMKIIδb clearly regulated Ito,f and the mRNA expression of its subunits. Likewise, calcineurin inhibition did not prevent the Ito,f reductions induced by β-AR stimulation despite strongly modulating Ito,f and subunit mRNA expression. In contrast, NF-κB inhibition partly rescued the ISO-mediated Ito,f reductions in association with restoration of KChIP2 mRNA expression. Consistent with these observations, KChIP2 promoter activity was reduced by p65 as well as β-AR stimulation. In conclusion, NF-κB, and not CaMKIIδ or calcineurin, partly mediates the Ito,f reductions induced by chronic β-AR stimulation. Both mRNA and KChIP2 promoter data suggest that the ISO-induced Ito,f reductions are, in part, mediated through reduced KChIP2 transcription caused by NF-κB activation.
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