Functional evolution of Erg potassium channel gating reveals an ancient origin for IKr

Alexandra S. Martinson, Damian B. Van Rossum, Fortunay H. Diatta, Michael J. Layden, Sarah A. Rhodes, Mark Q. Martindale, Timothy Jegla

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5712-5717
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number15
DOIs
StatePublished - Apr 15 2014

Fingerprint

Potassium Channels
Phenotype
Cnidaria
Drosophila
Ether
Sea Anemones
Voltage-Gated Potassium Channels
Caenorhabditis elegans
Prednisolone
Action Potentials
Sequence Analysis
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Martinson, Alexandra S. ; Van Rossum, Damian B. ; Diatta, Fortunay H. ; Layden, Michael J. ; Rhodes, Sarah A. ; Martindale, Mark Q. ; Jegla, Timothy. / Functional evolution of Erg potassium channel gating reveals an ancient origin for IKr. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 15. pp. 5712-5717.
@article{9189bc4f8f9a496bb974c8a7254b8dd5,
title = "Functional evolution of Erg potassium channel gating reveals an ancient origin for IKr",
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.",
author = "Martinson, {Alexandra S.} and {Van Rossum}, {Damian B.} and Diatta, {Fortunay H.} and Layden, {Michael J.} and Rhodes, {Sarah A.} and Martindale, {Mark Q.} and Timothy Jegla",
year = "2014",
month = "4",
day = "15",
doi = "10.1073/pnas.1321716111",
language = "English (US)",
volume = "111",
pages = "5712--5717",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "15",

}

Functional evolution of Erg potassium channel gating reveals an ancient origin for IKr. / Martinson, Alexandra S.; Van Rossum, Damian B.; Diatta, Fortunay H.; Layden, Michael J.; Rhodes, Sarah A.; Martindale, Mark Q.; Jegla, Timothy.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 15, 15.04.2014, p. 5712-5717.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Functional evolution of Erg potassium channel gating reveals an ancient origin for IKr

AU - Martinson, Alexandra S.

AU - Van Rossum, Damian B.

AU - Diatta, Fortunay H.

AU - Layden, Michael J.

AU - Rhodes, Sarah A.

AU - Martindale, Mark Q.

AU - Jegla, Timothy

PY - 2014/4/15

Y1 - 2014/4/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84898790124&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84898790124&partnerID=8YFLogxK

U2 - 10.1073/pnas.1321716111

DO - 10.1073/pnas.1321716111

M3 - Article

C2 - 24706772

AN - SCOPUS:84898790124

VL - 111

SP - 5712

EP - 5717

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 15

ER -