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Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2004 Jul 02; Vol. 279 (27), pp. 28187-96. Date of Electronic Publication: 2004 Apr 14. - Publication Year :
- 2004
-
Abstract
- It is widely thought that myogenin is one of the earliest detectable markers of skeletal muscle differentiation. Here we show that, during human myoblast differentiation, an inward rectifier K(+) channel (Kir2.1) and its associated hyperpolarization trigger expression and activity of the myogenic transcription factors, myogenin and myocyte enhancer factor-2 (MEF2). Furthermore, Kir2.1 current precedes and is required for the developmental increase in expression/activity of myogenin and MEF2. Drugs or antisense reducing Kir2.1 current diminished or suppressed fusion as well as expression/activity of myogenin and MEF2. In contrast, LY294002, an inhibitor of phosphatidylinositol 3-kinase (a pathway controlling initiation of the myogenic program) that inhibited both myogenin/MEF2 expression and fusion, did not affect Kir2.1 current. This non-blockade by LY294002 indicates that Kir2.1 acts upstream of myogenin and MEF2. We propose that Kir2.1 channel activation is a required key early event that initiates myogenesis by turning on myogenin and MEF2 transcription factors via a hyperpolarization-activated Ca(2+)-dependent pathway.
- Subjects :
- Blotting, Western
Calcium metabolism
Calibration
Cell Differentiation
Cell Division
Cells, Cultured
Chromones pharmacology
Electrophysiology
Genes, Reporter
Humans
Immunohistochemistry
Ions
Kinetics
MEF2 Transcription Factors
Membrane Potentials
Microscopy, Confocal
Microscopy, Fluorescence
Morpholines pharmacology
Myogenic Regulatory Factors
Oligonucleotides, Antisense metabolism
Phosphoinositide-3 Kinase Inhibitors
Potassium Channels, Inwardly Rectifying metabolism
Time Factors
Transcription, Genetic
Transfection
Cell Membrane metabolism
DNA-Binding Proteins biosynthesis
Myoblasts metabolism
Myogenin biosynthesis
Transcription Factors biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 279
- Issue :
- 27
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15084602
- Full Text :
- https://doi.org/10.1074/jbc.M313932200