

Other version: http://www.jbc.org/content/279/27/28187.full.pdf
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Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation |
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Published in | The Journal of biological chemistry. 2004, vol. 279, no. 27, p. 28187-28196 | |
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. | |
Keywords | Blotting, Western — Calcium/metabolism — Calibration — Cell Differentiation — Cell Division — Cell Membrane/ metabolism — Cells, Cultured — Chromones/pharmacology — DNA-Binding Proteins/ biosynthesis — Electrophysiology — Genes, Reporter — Humans — Immunohistochemistry — Ions — Kinetics — Membrane Potentials — Microscopy, Confocal — Microscopy, Fluorescence — Morpholines/pharmacology — Myoblasts/ metabolism — Myogenic Regulatory Factors — Myogenin/ biosynthesis — Oligonucleotides, Antisense/metabolism — Potassium Channels, Inwardly Rectifying/metabolism — Time Factors — Transcription Factors/ biosynthesis — Transcription, Genetic — Transfection | |
Identifiers | PMID: 15084602 | |
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Citation (ISO format) | KONIG, Stéphane et al. Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation. In: The Journal of biological chemistry, 2004, vol. 279, n° 27, p. 28187-28196. doi: 10.1074/jbc.M313932200 https://archive-ouverte.unige.ch/unige:10324 |