Journal article
Two Isoforms of the Mouse Ether-a-go-go –Related Gene Coassemble to Form Channels With Properties Similar to the Rapidly Activating Component of the Cardiac Delayed Rectifier K + Current
Circulation research, Vol.81(5), pp.870-878
11/1997
DOI: 10.1161/01.RES.81.5.870
PMID: 9351462
Abstract
HERG, the human ether-a-go-go-related gene, encodes a K(+)-selective channel with properties similar to the rapidly activating component of the delayed rectifier K+ current (IKr). Mutations of HERG cause the autosomal-dominant long-QT syndrome (LQTS), presumably by disrupting the normal function of IKr. The current produced by HERG is not identical to IKr, however, and the mechanism by which HERG mutations cause LQTS remains uncertain. To better define the role of Erg in the heart, we cloned Merg1 from mouse genomic and cardiac cDNA libraries. Merg1 has 16 exons and maps to mouse chromosome 5 in an area syntenic to human chromosome 7q, the map locus of HERG. We isolated three cardiac isoforms of Merg1: Merg1a is homologous to HERG and is expressed in heart, brain, and testes, Merg1a' lacks the first 59 amino acids of Merg1a and is not expressed abundantly, and Merg1b has a markedly shorter divergent N-terminal cytoplasmic domain and is expressed specifically in the heart. The Merg1 isoforms, like HERG, produce inwardly rectifying E-4031-sensitive currents when heterologously expressed in Xenopus oocytes. Merg1a and HERG produce currents with slow deactivation kinetics, whereas Merg1a' and Merg1b currents deactivate more rapidly. Merg1b coassembles with Merg1a to form channels with deactivation kinetics that are more rapid than those of Merg1a or HERG and nearly identical to IKr. In addition, a homologue of Merg1b is present in human cardiac and smooth muscle. Thus, we have identified a novel N-terminal Erg isoform that is expressed specifically in the heart, has rapid deactivation kinetics, and coassembles with the longer isoform in Xenopus oocytes. This N-terminal Erg isoform may determine the properties of IKr and contribute to the pathogenesis of LQTS.
Details
- Title: Subtitle
- Two Isoforms of the Mouse Ether-a-go-go –Related Gene Coassemble to Form Channels With Properties Similar to the Rapidly Activating Component of the Cardiac Delayed Rectifier K + Current
- Creators
- Barry London - From the Division of Cardiology (B.L., K.P.N., A.K.B.), University of Pittsburgh (Pa) Medical Center; the Department of Physiology (M.C.T., G.A.R.), University of Wisconsin Medical School, Madison; the Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.), ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Md; and the Central Research Division (C.A.S.), Pfizer Inc, Groton, ConnMatthew C Trudeau - From the Division of Cardiology (B.L., K.P.N., A.K.B.), University of Pittsburgh (Pa) Medical Center; the Department of Physiology (M.C.T., G.A.R.), University of Wisconsin Medical School, Madison; the Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.), ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Md; and the Central Research Division (C.A.S.), Pfizer Inc, Groton, ConnKimberly P Newton - From the Division of Cardiology (B.L., K.P.N., A.K.B.), University of Pittsburgh (Pa) Medical Center; the Department of Physiology (M.C.T., G.A.R.), University of Wisconsin Medical School, Madison; the Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.), ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Md; and the Central Research Division (C.A.S.), Pfizer Inc, Groton, ConnAnita K Beyer - From the Division of Cardiology (B.L., K.P.N., A.K.B.), University of Pittsburgh (Pa) Medical Center; the Department of Physiology (M.C.T., G.A.R.), University of Wisconsin Medical School, Madison; the Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.), ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Md; and the Central Research Division (C.A.S.), Pfizer Inc, Groton, ConnNeal G Copeland - From the Division of Cardiology (B.L., K.P.N., A.K.B.), University of Pittsburgh (Pa) Medical Center; the Department of Physiology (M.C.T., G.A.R.), University of Wisconsin Medical School, Madison; the Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.), ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Md; and the Central Research Division (C.A.S.), Pfizer Inc, Groton, ConnDebra J Gilbert - From the Division of Cardiology (B.L., K.P.N., A.K.B.), University of Pittsburgh (Pa) Medical Center; the Department of Physiology (M.C.T., G.A.R.), University of Wisconsin Medical School, Madison; the Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.), ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Md; and the Central Research Division (C.A.S.), Pfizer Inc, Groton, ConnNancy A. J enkins - From the Division of Cardiology (B.L., K.P.N., A.K.B.), University of Pittsburgh (Pa) Medical Center; the Department of Physiology (M.C.T., G.A.R.), University of Wisconsin Medical School, Madison; the Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.), ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Md; and the Central Research Division (C.A.S.), Pfizer Inc, Groton, ConnCarol A Satler - From the Division of Cardiology (B.L., K.P.N., A.K.B.), University of Pittsburgh (Pa) Medical Center; the Department of Physiology (M.C.T., G.A.R.), University of Wisconsin Medical School, Madison; the Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.), ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Md; and the Central Research Division (C.A.S.), Pfizer Inc, Groton, ConnGail A Robertson - From the Division of Cardiology (B.L., K.P.N., A.K.B.), University of Pittsburgh (Pa) Medical Center; the Department of Physiology (M.C.T., G.A.R.), University of Wisconsin Medical School, Madison; the Mammalian Genetics Laboratory (N.G.C., D.J.G., N.A.J.), ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Md; and the Central Research Division (C.A.S.), Pfizer Inc, Groton, Conn
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.81(5), pp.870-878
- DOI
- 10.1161/01.RES.81.5.870
- PMID
- 9351462
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 11/1997
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025686202771
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