Functional evolution of Erg potassium channel gating reveals an ancient origin for IKr
| Autor: | Timothy Jegla, Michael J. Layden, Damian B. van Rossum, Fortunay H. Diatta, Mark Q. Martindale, Alexandra S. Martinson, Sarah A. Rhodes |
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| Rok vydání: | 2014 |
| Předmět: |
Patch-Clamp Techniques
genetic structures Xenopus Molecular Sequence Data Action Potentials Gating Models Biological Evolution Molecular Species Specificity Repolarization Animals Placozoa Cloning Molecular Caenorhabditis elegans Genetics Multidisciplinary biology Base Sequence Models Genetic Reverse Transcriptase Polymerase Chain Reaction Computational Biology Depolarization Cardiac action potential Bayes Theorem Sequence Analysis DNA Biological Sciences biology.organism_classification Phenotype Potassium channel eye diseases Ether-A-Go-Go Potassium Channels Cell biology Sea Anemones Daphnia Caenorhabditis sense organs Erg Ion Channel Gating |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 111(15) |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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