ArticlePloS one2010
Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr) and modulates cardiac action potential characteristics.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Cell Line and Media Composition Influence the Production of Giant Plasma Membrane Vesicles.ACS biomaterials science & engineering · 2024Article
- hERG1 channel subunit composition mediates proton inhibition of rapid delayed rectifier potassium current (IThe Journal of biological chemistry · 2023Article
- The ERG1 KFrontiers in molecular neuroscience · 2022Review
- Conformation-sensitive antibody reveals an altered cytosolic PAS/CNBh assembly during hERG channel gating.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Fluid flow modulates electrical activity in cardiac hERG potassium channels.The Journal of biological chemistry · 2018Article
- Determinants of Isoform-Specific Gating Kinetics of hERG1 Channel: Combined Experimental and Simulation Study.Frontiers in physiology · 2018Article
- hERG1a and hERG1b potassium channel subunits directly interact and preferentially form heteromeric channels.The Journal of biological chemistry · 2017Article
- Modulation of KBritish journal of pharmacology · 2017Article
- Dominant negative consequences of a hERG 1b-specific mutation associated with intrauterine fetal death.Progress in biophysics and molecular biology · 2016Article
- hERG 1b is critical for human cardiac repolarization.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Concerted all-or-none subunit interactions mediate slow deactivation of human ether-à-go-go-related gene K+ channels.The Journal of biological chemistry · 2014Article
- Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are inhibited by mGluR1 activation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Ionic mechanisms limiting cardiac repolarization reserve in humans compared to dogs.The Journal of physiology · 2013Article
- The eag domain regulates hERG channel inactivation gating via a direct interaction.The Journal of general physiology · 2013Article
- Models of HERG gating.Biophysical journal · 2011Article
- Differential effects of Kv11.1 activators on Kv11.1a, Kv11.1b and Kv11.1a/Kv11.1b channels.British journal of pharmacology · 2010Article
- Role of ERG1 isoforms in modulation of ERG1 channel trafficking and function.Pflugers Archiv : European journal of physiology · 2010Review
- A stable cell line inducibly expressing hERG1a/1b heteromeric channels.Journal of pharmacological and toxicological methodsArticle
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe repolarizing cardiac rapid delayed rectifier current, I(Kr), is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr). Marked heterogeneity in the kinetic properties of native I(Kr) has been described. We hypothesized that the heterogeneity of native I(Kr) can be reproduced by differential expression of ERG1a and ERG1b isoforms. Furthermore, the functional consequences of differential expression of ERG1 isoforms were explored as a potential mechanism underlying native heterogeneity of action potential duration (APD) and restitution. METHODOLOGY/PRINCIPAL
findingsThe results show that the heterogeneity of native I(Kr) can be reproduced in heterologous expression systems by differential expression of ERG1a and ERG1b isoforms. Characterization of the macroscopic kinetics of ERG1 currents demonstrated that these were dependent on the relative abundance of ERG1a and ERG1b. Furthermore, we used a computational model of the ventricular cardiomyocyte to show that both APD and the slope of the restitution curve may be modulated by varying the relative abundance of ERG1a and ERG1b. As the relative abundance of ERG1b was increased, APD was gradually shortened and the slope of the restitution curve was decreased. CONCLUSIONS/SIGNIFICANCE: Our results show that differential expression of ERG1 isoforms may explain regional heterogeneity of I(Kr) kinetics. The data demonstrate that subunit dependent changes in channel kinetics are important for the functional properties of ERG1 currents and hence I(Kr). Importantly, our results suggest that regional differences in the relative abundance of ERG1 isoforms may represent a potential mechanism underlying the heterogeneity of both APD and APD restitution observed in mammalian hearts.
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