ArticleThe Journal of physiology2007
Modulation of hERG potassium currents in HEK-293 cells by protein kinase C. Evidence for direct phosphorylation of pore forming subunits.
Article in The Journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 57 citations in OpenAlex.
- Sudden death-associated KCNH2 variants exert opposing effects on a nuclear subdomain of the cardiac potassium channel hERG1.The Journal of biological chemistry · 2026Article
- Sudden Death-AssociatedbioRxiv : the preprint server for biology · 2025Article
- Obesity Arrhythmias: Role of IL-6 Trans-Signaling.International journal of molecular sciences · 2024Review
- Locus Coeruleus Neurons' Firing Pattern Is Regulated by ERG Voltage-Gated KInternational journal of molecular sciences · 2022Article
- Spike Afterhyperpolarizations Govern Persistent Firing Dynamics in Rat Neocortical and Hippocampal Pyramidal Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Electrophysiological characterization of the modified hERGPhysiological reports · 2020Article
- Altered KCanadian journal of physiology and pharmacology · 2019Article
- Selective attenuation of Ether-a-go-go related KeLife · 2019Article
- Altered Repolarization Reserve in Failing Rabbit Ventricular Myocytes: Calcium and β-Adrenergic Effects on Delayed- and Inward-Rectifier Potassium Currents.Circulation. Arrhythmia and electrophysiology · 2018Article
- Modulation of Ether-à-Go-Go Related Gene (ERG) Current Governs Intrinsic Persistent Activity in Rodent Neocortical Pyramidal Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Different protein kinase C isoenzymes mediate inhibition of cardiac rapidly activating delayed rectifier KBritish journal of pharmacology · 2017Article
- Mechanisms of Persistent Activity in Cortical Circuits: Possible Neural Substrates for Working Memory.Annual review of neuroscience · 2017Review
- Evolution of strategies to improve preclinical cardiac safety testing.Nature reviews. Drug discovery · 2016Review
- Functional cross-talk between the α1- and β1-adrenergic receptors modulates the rapidly activating delayed rectifier potassium current in guinea pig ventricular myocytes.International journal of molecular sciences · 2014Article
- Long-term channel block is required to inhibit cellular transformation by human ether-à-go-go-related gene (hERG1) potassium channels.Molecular pharmacology · 2014Article
- A novel cellular stress response characterised by a rapid reorganisation of membranes of the endoplasmic reticulum.Cell death and differentiation · 2012Article
- Long QT2 mutation on the Kv11.1 ion channel inhibits current activity by ablating a protein kinase Cα consensus site.Molecular pharmacology · 2012Article
- Suppression of phosphoinositide 3-kinase signaling and alteration of multiple ion currents in drug-induced long QT syndrome.Science translational medicine · 2012Article
- Cell type influences the molecular mechanisms involved in hormonal regulation of ERG K+ channels.Pflugers Archiv : European journal of physiology · 2012Article
- Cytoplasmic domains and voltage-dependent potassium channel gating.Frontiers in pharmacology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The human ether-a-go-go related gene (hERG) potassium channel is expressed in a variety of tissues including the heart, neurons and some cancer cells. hERG channels are modulated by several intracellular signalling pathways and these provide important mechanisms for regulating cellular excitability. In this study, we investigated muscarinic modulation of hERG currents and direct phosphorylation of channel subunits expressed in HEK-293 cells at physiologically relevant temperatures by protein kinase C (PKC). Activation of G(alpha q/11)-coupled M(3)-muscarinic receptors with methacholine, reduced current amplitudes at all potentials with minor effects on the voltage dependence of activation and inactivation. The response to methacholine was insensitive to intracellular BAPTA, but was attenuated by either acute inhibition of PKC with 300 nm bisindolylmaleimide-1 (bis-1) or chronic down-regulation of PKC isoforms by 24 h pretreatment of cells with phorbol 12-myristate 13-acetate (PMA). Stimulation of PKC with 1-oleoyl 2-acetylglycerol (OAG), an analogue of diacylglycerol (DAG), mimicked the actions of muscarinic receptor stimulation. Direct phosphorylation of hERG was measured by [(32)P]orthophosphate labelling of immunoprecipitated protein with an anti-hERG antibody. Basal phosphorylation was high in unstimulated cells and further increased by OAG. The OAG dependent increase was abolished by bis-1 and down-regulation of PKC, but basal levels of phosphorylation were unchanged. Deletion of the amino-terminus of hERG prevented both the modulation of channel activity and the increase of phosphorylation by OAG. Our results are consistent with calcium and/or DAG sensitive isotypes of PKC modulating hERG currents through a mechanism that involves direct phosphorylation of sites on the amino terminus of hERG.
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