ArticleProceedings of the National Academy of Sciences of the United States of America2014
Functional evolution of Erg potassium channel gating reveals an ancient origin for IKr.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 52 citations in OpenAlex.
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- Neurite branching is associated with mixed microtubule polarity in sea anemone neurons.The Journal of experimental biology · 2025Article
- Modulation ofInternational journal of molecular sciences · 2025Article
- Ctenophores and parahoxozoans independently evolved functionally diverse voltage-gated K+ channels.The Journal of general physiology · 2025Article
- A broad survey of choanoflagellates revises the evolutionary history of the Shaker family of voltage-gated KProceedings of the National Academy of Sciences of the United States of America · 2024Article
- An intracellular hydrophobic nexus critical for hERG1 channel slow deactivation.Biophysical journal · 2024Article
- Genome-Scale Analysis Reveals Extensive Diversification of Voltage-Gated K+ Channels in Stem Cnidarians.Genome biology and evolution · 2023Article
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- Effective Perturbations by Small-Molecule Modulators on Voltage-Dependent Hysteresis of Transmembrane Ionic Currents.International journal of molecular sciences · 2022Review
- The Effectiveness of Isoplumbagin and Plumbagin in Regulating Amplitude, Gating Kinetics, and Voltage-Dependent Hysteresis ofBiomedicines · 2022Article
- Efficient expression of a cnidarian peptide-gated ion channel in mammalian cells.Channels (Austin, Tex.) · 2021Article
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- Cytoskeletal and synaptic polarity of LWamide-like+ ganglion neurons in the sea anemoneThe Journal of experimental biology · 2020Article
- Characterization of the Synergistic Inhibition ofInternational journal of molecular sciences · 2020Article
- Genome-Wide Association and Prediction of Traits Related to Salt Tolerance in Autotetraploid Alfalfa (International journal of molecular sciences · 2020Article
- Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, ofInternational journal of molecular sciences · 2020Article
- The S6 gate in regulatory Kv6 subunits restricts heteromeric KThe Journal of general physiology · 2018Article
- How an intrinsic ligand tunes the activity of a potassium channel.The Journal of general physiology · 2018Article
- Article
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7 authors at 3 institutions in 1 country.
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Abstract
Mammalian Ether-a-go-go related gene (Erg) family voltage-gated K(+) channels possess an unusual gating phenotype that specializes them for a role in delayed repolarization. Mammalian Erg currents rectify during depolarization due to rapid, voltage-dependent inactivation, but rebound during repolarization due to a combination of rapid recovery from inactivation and slow deactivation. This is exemplified by the mammalian Erg1 channel, which is responsible for IKr, a current that repolarizes cardiac action potential plateaus. The Drosophila Erg channel does not inactivate and closes rapidly upon repolarization. The dramatically different properties observed in mammalian and Drosophila Erg homologs bring into question the evolutionary origins of distinct Erg K(+) channel functions. Erg channels are highly conserved in eumetazoans and first evolved in a common ancestor of the placozoans, cnidarians, and bilaterians. To address the ancestral function of Erg channels, we identified and characterized Erg channel paralogs in the sea anemone Nematostella vectensis. N. vectensis Erg1 (NvErg1) is highly conserved with respect to bilaterian homologs and shares the IKr-like gating phenotype with mammalian Erg channels. Thus, the IKr phenotype predates the divergence of cnidarians and bilaterians. NvErg4 and Caenorhabditis elegans Erg (unc-103) share the divergent Drosophila Erg gating phenotype. Phylogenetic and sequence analysis surprisingly indicates that this alternate gating phenotype arose independently in protosomes and cnidarians. Conversion from an ancestral IKr-like gating phenotype to a Drosophila Erg-like phenotype correlates with loss of the cytoplasmic Ether-a-go-go domain. This domain is required for slow deactivation in mammalian Erg1 channels, and thus its loss may partially explain the change in gating phenotype.
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